Five Layers of Receptor Signaling in Î³Î´ T-Cell Differentiation and Activation

Ribeiro, SÃ©rgio T.; Ribot, Julie C.; Silva-Santos, Bruno

doi:10.3389/fimmu.2015.00015

Cited by 116T-cell and B-cell ImmunologyImmune Cell Function and InteractionPsoriasis: Treatment and Pathogenesis

Five Layers of Receptor Signaling in Î³Î´ T-Cell Differentiation and Activation

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Ribeiro, SÃ©rgio T., Ribot, Julie C., Silva-Santos, Bruno·2015·Frontiers in Immunology

DOI 10.3389/fimmu.2015.00015PMC PMC4306313

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Abstract

The contributions of γδ T-cells to immunity to infection or tumors critically depend on their activation and differentiation into effectors capable of secreting cytokines and killing infected or transformed cells. These processes are molecularly controlled by surface receptors that capture key extracellular cues and convey downstream intracellular signals that regulate γδ T-cell physiology. The understanding of how environmental signals are integrated by γδ T-cells is critical for their manipulation in clinical settings. Here, we discuss how different classes of surface receptors impact on human and murine γδ T-cell differentiation, activation, and expansion. In particular, we review the role of five receptor types: the T-cell receptor (TCR), costimulatory receptors, cytokine receptors, NK receptors, and inhibitory receptors. Some of the key players are the costimulatory receptors CD27 and CD28, which differentially impact on pro-inflammatory subsets of γδ T-cells; the cytokine receptors IL-2R, IL-7R, and IL-15R, which drive functional differentiation and expansion of γδ T-cells; the NK receptor NKG2D and its contribution to γδ T-cell cytotoxicity; and the inhibitory receptors PD-1 and BTLA that control γδ T-cell homeostasis. We discuss these and other receptors in the context of a five-step model of receptor signaling in γδ T-cell differentiation and activation, and discuss its implications for the manipulation of γδ T-cells in immunotherapy.

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IL-12 and IL-18 promote IFN-γ production, while IL-1β and IL-23 drive γδ T cells towards IL-17-producing cells.
“IL-12 and IL-18 promote IFN-γ production, while IL-1β and IL-23 drive them towards IL-17-producing cells (14).”
From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [14]

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Cutting Edge: Adaptive Versus Innate Receptor Signals Selectively Control the Pool Sizes of Murine IFN-γ– or IL-17–Producing γδ T Cells upon Infection
Ribot, J. C., Chaves‐Ferreira, M., d’Orey, F., Wencker, M., Gonçalves‐Sousa, N., Decalf, J., Simas, J. P., Hayday, A., & Silva‐Santos, B. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002283 · Cited by 99 · see citing works
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IL-15 enhances the response of human gamma delta T cells to nonpeptide [correction of nonpetide] microbial antigens.
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The Inhibitory Receptor BTLA Controls γδ T Cell Homeostasis and Inflammatory Responses
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IL-15 Enhances the Response of Human γδ T Cells to Nonpetide Microbial Antigens
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NKG2D Costimulates Human Vγ9Vδ2 T Cell Antitumor Cytotoxicity through Protein Kinase Cθ-Dependent Modulation of Early TCR-Induced Calcium and Transduction Signals
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IL-23R and TCR signaling drives the generation of neonatal Vγ9Vδ2 T cells expressing high levels of cytotoxic mediators and producing IFN-γ and IL-17
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IL-7 Produced by Thymic Epithelial Cells Plays a Major Role in the Development of Thymocytes and TCRγδ+ Intraepithelial Lymphocytes
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B7–CD28 Costimulatory Signals Control the Survival and Proliferation of Murine and Human γδ T Cells via IL-2 Production
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Siva-1 binds to and inhibits BCL-X L -mediated protection against UV radiation-induced apoptosis
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Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression
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γδ T Cell Homeostasis Is Controlled by IL-7 and IL-15 Together with Subset-Specific Factors
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Costimulation Signals for Memory CD8+ T Cells During Viral Infections
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An architectural perspective on signaling by the pre‐, αβ and γδ T cell receptors
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Drug-Induced Expansion and Differentiation of Vγ9Vδ2 T Cells In Vivo: The Role of Exogenous IL-2
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Different composition of the human and the mouse γδ T cell receptor explains different phenotypes of CD3γ and CD3δ immunodeficiencies
Siegers, G. M., Swamy, M., Fernández-Malavé, E., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070782 · Cited by 75 · see citing works
Piecing together the family portrait of TCR ‐ CD 3 complexes
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IL-21-Mediated Potentiation of Antitumor Cytolytic and Proinflammatory Responses of Human Vγ9Vδ2 T Cells for Adoptive Immunotherapy
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PD-1 coinhibitory signals: the link between pathogenesis and protection
Kulpa, D. A., Lawani, M., Cooper, A., Peretz, Y., Ahlers, J., & Sékaly, R.-P. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.02.002 · Cited by 70 · see citing works
Searching for “signal 2”: costimulation requirements of γδ T cells
Ribot, J. C., deBarros, A., & Silva‐Santos, B. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0698-2 · Cited by 68 · see citing works
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γδ T cell subsets: A link between TCR and function?
O’Brien, R. L., & Born, W. K. (2010) · Seminars in Immunology · doi:10.1016/j.smim.2010.03.006 · Cited by 66 · see citing works
NKG2D Ligation without T Cell Receptor Engagement Triggers Both Cytotoxicity and Cytokine Production in Dendritic Epidermal T Cells
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Effect of IL-18 on Expansion of γδ T Cells Stimulated by Zoledronate and IL-2
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Interleukin 15 controls the generation of the restricted T cell receptor repertoire of γδ intestinal intraepithelial lymphocytes
Zhao, H., Nguyen, H. V., & Kang, J. (2005) · Nature Immunology · doi:10.1038/ni1267 · Cited by 63 · see citing works
Grb2 and Gads Exhibit Different Interactions with CD28 and Play Distinct Roles in CD28-Mediated Costimulation
Watanabe, R., Harada, Y., Takeda, K., Takahashi, J., Ohnuki, K., Ogawa, S., Ohgai, D., Kaibara, N., Koiwai, O., Tanabe, K., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.1085 · Cited by 62 · see citing works
The Role of Coinhibitory Signaling Pathways in Transplantation and Tolerance
McGrath, M. M., & Najafian, N. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00047 · Cited by 62 · see citing works
The Common Cytokine Receptor γ Chain Controls Survival of γ/δ T Cells
Malissen, M., Pereira, P., Gerber, D. J., MALISSEN, B., & Santo, J. P. D. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.8.1277 · Cited by 62 · see citing works
HIV envelope-mediated, CCR5/α4β7-dependent killing of CD4-negative γδ T cells which are lost during progression to AIDS
Li, H., & Pauza, C. D. (2011) · Blood · doi:10.1182/blood-2011-05-356535 · Cited by 61 · see citing works
Human Vγ9Vδ2 T cells: From signals to functions
Nédellec, S., Bonneville, M., & Scotet, E. (2010) · Seminars in Immunology · doi:10.1016/j.smim.2010.04.004 · Cited by 61 · see citing works
CD28 stimulation triggers NF- B activation through the CARMA1-PKC -Grb2/Gads axis
Takeda, K., Harada, Y., Watanabe, R., Inutake, Y., Ogawa, S., Onuki, K., Kagaya, S., Tanabe, K., Kishimoto, H., & Abe, R. (2008) · International Immunology · doi:10.1093/intimm/dxn108 · Cited by 58 · see citing works
Early IL-17 Production by Intrahepatic T Cells Is Important for Adaptive Immune Responses in Viral Hepatitis
Hou, L., Jie, Z., Desai, M. M., Liang, Y., Soong, L., Wang, T., & Sun, J. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201970 · Cited by 56 · see citing works
Origins of γδ T Cell Effector Subsets: A Riddle Wrapped in an Enigma
Fahl, S. P., Coffey, F. J., & Wiest, D. L. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401813 · Cited by 55 · see citing works
Highly Active Microbial Phosphoantigen Induces Rapid yet Sustained MEK/Erk- and PI-3K/Akt-Mediated Signal Transduction in Anti-Tumor Human γδ T-Cells
Correia, D. V., d’Orey, F., Cardoso, B. A., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005657 · Cited by 51 · see citing works
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T cell receptor signalling in γδ cell development: strength isn’t everything
Turchinovich, G., & Pennington, D. J. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.09.005 · Cited by 50 · see citing works
Versatile signaling through NKG2D
Long, E. O. (2002) · Nature Immunology · doi:10.1038/ni1202-1119 · Cited by 42 · see citing works
Involvement of CD56brightCD11c+ Cells in IL-18–Mediated Expansion of Human γδ T Cells
Tsuda, J., Li, W., Yamanishi, H., Yamamoto, H., Okuda, A., Kubo, S., Ma, Z., Terada, N., Tanaka, Y., & Okamura, H. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001919 · Cited by 38 · see citing works
CD30L/CD30 is critical for maintenance of IL-17A-producing γδ T cells bearing Vγ6 in mucosa-associated tissues in mice
Sun, X., Shibata, K., Yamada, H., Guo, Y. J., Muta, H., Podack, E. R., & Yoshikai, Y. (2013) · Mucosal Immunology · doi:10.1038/mi.2013.18 · Cited by 33 · see citing works
4–1 BB signal stimulates the activation, expansion, and effector functions of γδ T cells in mice and humans
Lee, S. J., Kim, Y. H., Hwang, S. H., et al. (2013) · European Journal of Immunology · doi:10.1002/eji.201242842 · Cited by 31 · see citing works
γδ T Cell Receptors without a Job
Kapsenberg, M. L. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.004 · Cited by 30 · see citing works
NF-κB Modulates Sensitivity to Apoptosis, Proinflammatory and Migratory Potential in Short- versus Long-Term Cultured Human γδ Lymphocytes
Ferrarini, M., Delfanti, F., Gianolini, M. E., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.9.5857 · Cited by 30 · see citing works
Interleukin-15 effectively potentiates the in vitro tumor-specific activity and proliferation of peripheral blood γδT cells isolated from glioblastoma patients
Yamaguchi, T., Suzuki, Y., Katakura, R., Ebina, T., Yokoyama, J., & Fujimiya, Y. (1998) · Cancer Immunology Immunotherapy · doi:10.1007/s002620050509 · Cited by 28 · see citing works
Involvement of Classical and Novel Protein Kinase C Isoforms in the Response of Human Vγ9Vδ2 T Cells to Phosphate Antigens
Cipriani, B., Knowles, H., Chen, L., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.10.5761 · Cited by 22 · see citing works
Different composition of the human and the mouse γδ T cell receptor explains different phenotypes of CD3γ and CD3δ immunodeficiencies
Siegers, G. M., Swamy, M., Fernández-Malavé, E., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070782102207c · Cited by 21 · see citing works
γδ T Cells Acquire Effector Fates in the Thymus and Differentiate into Cytokine-Producing Effectors in a Listeria Model of Infection Independently of CD28 Costimulation
Laird, R. M., Wolf, B. J., Princiotta, M. F., & Hayes, S. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063178 · Cited by 19 · see citing works
Differential survival of γδT cells, αβT cells and NK cells upon engagement of NKG2D by NKG2DL‐expressing leukemic cells
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Interplay of T-cell receptor and interleukin-2 signalling in Vγ2Vδ2 T-cell cytotoxicity
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CD30 ligation differentially affects CXCR4‐dependent HIV‐1 replication and soluble CD30 secretion in non‐Hodgkin cell lines and in γ δ T lymphocytes
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NKp44L
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The Role of LAT–PLCγ1 Interaction in γδ T Cell Development and Homeostasis
Sullivan, S. A., Zhu, M., Bao, S., Lewis, C. A., Ou-Yang, C.-W., & Zhang, W. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302493 · Cited by 11 · see citing works
The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2
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Biswas, 2000, Engagement of CD30 shapes the secretion of cytokines by human gamma delta T cells, Eur J Immunol, 30, 2172, 10.1002/1521-4141(2000)30:182172::aid-immu21723.0.co;2-5 · DOI

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Early Immune Pathology and Persistent Dysregulation Characterise Severe COVID-19
Bergamaschi, L., Mescia, F., Turner, L., Hanson, A., Kotagiri, P., Dunmore, B. J., Ruffieux, H., Sa, A. D., Huhn, O., Morgan, M. D., et al. (2020) · Immunity · doi:10.1016/j.immuni.2021.05.010 · Cited by 323 · see citing works
“Similar, though less well defined, bystander phenomena occur in CD4, MAIT, and gd T cell responses (Holzapfel et al., 2014; Ribeiro et al., 2015; Ussher et al., 2018).”
Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection
Shandilya, S., Kumar, S., Jha, N. K., Kesari, K. K., & Ruokolainen, J. (2021) · Journal of Advanced Research · doi:10.1016/j.jare.2021.09.005 · Cited by 300 · see citing works
NF-kappaB: Two Sides of the Same Coin
Pires, B. R. B., Silva, R. C. M. C., Ferreira, G. M., & Abdelhay, E. S. F. W. (2018) · Genes · doi:10.3390/genes9010024 · Cited by 235 · see citing works
Delta One T Cells for Immunotherapy of Chronic Lymphocytic Leukemia: Clinical-Grade Expansion/Differentiation and Preclinical Proof of Concept
Almeida, A. R. M., Correia, D. V., Fernandes‐Platzgummer, A., da Silva, C. L., da Silva, M. G., Anjos, D. R., & Silva‐Santos, B. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0597 · Cited by 229 · see citing works
“In contrast, key inhibitory and exhaustion-associated molecules such as PD-1, CTLA-4, or CD94 (24) were expressed either at very low levels or not expressed at all (Fig.”
BackgroundSelf-citation
Key Features of Gamma-Delta T-Cell Subsets in Human Diseases and Their Immunotherapeutic Implications
Lawand, M., Déchanet‐Merville, J., & Dieu‐Nosjean, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00761 · Cited by 222 · see citing works
Function of γδ T cells in tumor immunology and their application to cancer therapy
Park, J. H., & Lee, H. K. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00576-0 · Cited by 191 · see citing works
Improving the Efficiency of Vγ9Vδ2 T-Cell Immunotherapy in Cancer
Hoeres, T., Smetak, M., Pretscher, D., & Wilhelm, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00800 · Cited by 154 · see citing works
γδ T cell responses: How many ligands will it take till we know?
Vermijlen, D., Gatti, D., Kouzeli, A., Rus, T., & Eberl, M. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.10.009 · Cited by 111 · see citing works
Regulation of γδ T Cell Effector Diversification in the Thymus
Parker, M. E., & Ciofani, M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00042 · Cited by 99 · see citing works
“As innate-like lymphocytes, γδ T cells sense their local environment and are regulated through a combination of the TCR, cytokine receptors, co-stimulatory receptors, inhibitory receptors, and natural killer receptors (15).”
Background
Dendritic Cells and Programmed Death-1 Blockade: A Joint Venture to Combat Cancer
Versteven, M., den Bergh, J. M. J. V., Marcq, E., Smits, E., Tendeloo, V. F. V., Hobo, W. A., & Lion, E. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00394 · Cited by 97 · see citing works
“Expression of PD-1 is also demonstrated on γδ T cells (62) and resulted in γδ T cell exhaustion that could be overcome by administration of a blocking anti-PD-L1 antibody (63, 64).”
Background
Characterization of γδ T Cells from Zebrafish Provides Insights into Their Important Role in Adaptive Humoral Immunity
Wan, F., Hu, C., Ma, J.-X., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00675 · Cited by 95 · see citing works
IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer
Kourko, O., Seaver, K., Odoardi, N., Basta, S., & Gee, K. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00969 · Cited by 94 · see citing works
Molecular Determinants of Target Cell Recognition by Human γδ T Cells
Simões, A. E. S., Lorenzo, B. D., & Silva‐Santos, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00929 · Cited by 91 · see citing works
“Furthermore, γδ T cells bear a plethora of NK cell receptors (NKRs) on their surface, which allow for very fast responses against infected or transformed cells (3), thus contributing to a first line of defense that precedes antigen-specific αβ T-cell responses (4).”
BackgroundSelf-citation
Comparing Mouse and Human Tissue-Resident γδ T Cells
Qu, G., Wang, S., Zhou, Z., Jiang, D., Liao, A., & Luo, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.891687 · Cited by 87 · see citing works
γδ T Cells Promote Steatohepatitis by Orchestrating Innate and Adaptive Immune Programming
Torres‐Hernandez, A., Wang, W., Nikiforov, Y., Tejada, K., Torres, L., Kalabin, A., Adam, S., Wu, J., Lu, L., Chen, R., et al. (2020) · Hepatology · doi:10.1002/hep.30952 · Cited by 80 · see citing works
γδT cells suppress liver fibrosis via strong cytolysis and enhanced NK cell-mediated cytotoxicity against hepatic stellate cells
Liu, M., Hu, Y., Yuan, Y., Tian, Z., & Zhang, C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00477 · Cited by 65 · see citing works
Human Peripheral Blood Gamma Delta T Cells: Report on a Series of Healthy Caucasian Portuguese Adults and Comprehensive Review of the Literature
Fonseca, S., Pereira, V., Lau, C., Teixeira, M. D. A., Antunes, M. B., & Lima, M. (2020) · Cells · doi:10.3390/cells9030729 · Cited by 65 · see citing works
Role of γδ T cells in controlling viral infections with a focus on influenza virus: implications for designing novel therapeutic approaches
Sabbaghi, A., Miri, S. M., Keshavarz, M., Mahooti, M., Zebardast, A., & Ghaemi, A. (2020) · Virology Journal · doi:10.1186/s12985-020-01449-0 · Cited by 62 · see citing works
Identification of distinct functional thymic programming of fetal and pediatric human γδ thymocytes via single-cell analysis
Sanchez, G. S., Papadopoulou, M., Azouz, A., Tafesse, Y., Mishra, A., Chan, J. K. Y., Fan, Y., Verdebout, I., Porco, S., Libert, F., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33488-2 · Cited by 61 · see citing works
The Ugly Duckling Turned to Swan: A Change in Perception of Bystander-Activated Memory CD8 T Cells
Maurice, N. J., Taber, A. K., & Prlic, M. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2000937 · Cited by 59 · see citing works
Dual Face of Vγ9Vδ2-T Cells in Tumor Immunology: Anti- versus Pro-Tumoral Activities
Xiang, Z., & Tu, W. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01041 · Cited by 60 · see citing works
Engineering γδT cells limits tonic signaling associated with chimeric antigen receptors
Fisher, J. P. H., Sharma, R., Don, D. W., Barisa, M., Hurtado, M. O., Abramowski, P., Porter, L., Day, W. P., Borea, R., Inglott, S., et al. (2019) · Science Signaling · doi:10.1126/scisignal.aax1872 · Cited by 50 · see citing works
Interleukin-15-Cultured Dendritic Cells Enhance Anti-Tumor Gamma Delta T Cell Functions through IL-15 Secretion
Acker, H. H. V., Anguille, S., Reu, H. D., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00658 · Cited by 49 · see citing works
IL-2 and IL-15 blockade by BNZ-1, an inhibitor of selective γ-chain cytokines, decreases leukemic T-cell viability
Wang, T. T., Yang, J., Zhang, Y., et al. (2018) · Leukemia · doi:10.1038/s41375-018-0290-y · Cited by 49 · see citing works
Gamma/Delta T Cells and Their Role in Protection Against Malaria
Deroost, K., & Langhorne, J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02973 · Cited by 46 · see citing works
Vγ9Vδ2 T Cells Concurrently Kill Cancer Cells and Cross-Present Tumor Antigens
Olofsson, G. H., Idorn, M., Simões, A. M. C., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.645131 · Cited by 47 · see citing works
“(C) Vg9Vd2 T cell percentage expression of NKG2D, CD56, CD16, and DNAM-1 is shown.”
BackgroundInfluential
Hypoxia regulates the differentiation and anti-tumor effector functions of γδT cells in oral cancer
Sureshbabu, S. K., Chaukar, D. A., & Chiplunkar, S. V. (2020) · Clinical & Experimental Immunology · doi:10.1111/cei.13436 · Cited by 46 · see citing works
Diversity in recognition and function of human γδ T cells
Castro, C. D., Boughter, C. T., Broughton, A. E., Ramesh, A., & Adams, E. J. (2020) · Immunological Reviews · doi:10.1111/imr.12930 · Cited by 44 · see citing works
T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease
Gebru, Y., Gupta, H., Kim, H. S., Eom, J. A., Kwon, G., Park, E., Jeong, J.-J., Won, S., Sharma, S., Ganesan, R., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212190 · Cited by 30 · see citing works
IL-12 Expands and Differentiates Human Vγ2Vδ2 T Effector Cells Producing Antimicrobial Cytokines and Inhibiting Intracellular Mycobacterial Growth
Yang, R., Yao, L., Shen, L., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00913 · Cited by 40 · see citing works
“Nevertheless, the IL-12-STAT4 and PI3K/AKT pathways are quite different from the IL-2 signaling pathway or mechanisms (20, 21).”
Background
Editorial: “Recent advances in gamma/delta T cell biology: new ligands, new functions, and new translational perspectives”
Kabelitz, D. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00371 · Cited by 40 · see citing works
“IL-7 also supports homeostatic proliferation of γδ T cells and regulates surface expression of BTLA in a STAT5-dependent manner (1).”
BackgroundMethodInfluential
Differentiation and functional plasticity of gamma-delta (γδ) T cells under homeostatic and disease conditions
Giri, S., & Lal, G. (2021) · Molecular Immunology · doi:10.1016/j.molimm.2021.06.006 · Cited by 37 · see citing works
The Diverse Roles of γδ T Cells in Cancer: From Rapid Immunity to Aggressive Lymphoma
Schönefeldt, S., Wais, T., Herling, M., Mustjoki, S. M., Bekiaris, V., Moriggl, R., & Neubauer, H. A. (2021) · Cancers · doi:10.3390/cancers13246212 · Cited by 39 · see citing works
The Aging of γδ T Cells
Xu, W., Lau, Z. W. X., Fülöp, T., & Larbi, A. (2020) · Cells · doi:10.3390/cells9051181 · Cited by 35 · see citing works
“Studies have shown that γδ T cell subsets are able to respond to IL-12, IL-15, IL-18 which then leads to activation, the secretion of cytokines and proliferation [139].”
Background
Costimulation of γδTCR and TLR7/8 promotes Vδ2 T-cell antitumor activity by modulating mTOR pathway and APC function
Wang, H., Chen, H., Liu, S., Zhang, J., Lu, H., Somasundaram, R., Choi, R., Zhang, G., Ou, L., Scholler, J., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003339 · Cited by 35 · see citing works
Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination
Angel, C. J. L., Pham, E. A., Du, H., Vallania, F., Fram, B. J., Pérez, K., Nguyen, T., Rosenberg‐Hasson, Y., Ahmed, A., Dekker, C. L., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2022928118 · Cited by 33 · see citing works
γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends
Barros, M. D. S., de Araújo, N. D., Magalhães-Gama, F., Pereira-Ribeiro, T. L., Alves-Hanna, F. S., Tarragô, A. M., Malheiro, A., & Costa, A. G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.729085 · Cited by 33 · see citing works
Systemic Characterization of Novel Immune Cell Phenotypes in Recurrent Pregnancy Loss
Liu, H., Lin, X., Huang, X., Huang, D., Song, S., Chen, Y.-J., Tang, J., Tao, D., Yin, Z., Mor, G., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.657552 · Cited by 32 · see citing works
In the Absence of a TCR Signal IL-2/IL-12/18-Stimulated γδ T Cells Demonstrate Potent Anti-Tumoral Function Through Direct Killing and Senescence Induction in Cancer Cells
Schilbach, K., Welker, C., Krickeberg, N., Kaißer, C., Schleicher, S., & Hashimoto, H. (2020) · Cancers · doi:10.3390/cancers12010130 · Cited by 31 · see citing works
Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells
Domae, E., Hirai, Y., Ikeo, T., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.17498 · Cited by 31 · see citing works
“This is consistent with the characteristics of Vγ9Vδ2 T cells which are considered as innate-like T lymphocyte with NK cell characteristics [34].”
Result
Bortezomib enhances cytotoxicity of ex vivo-expanded gamma delta T cells against acute myeloid leukemia and T-cell acute lymphoblastic leukemia
Story, J. Y., Zoine, J. T., Burnham, R. E., et al. (2020) · Cytotherapy · doi:10.1016/j.jcyt.2020.09.010 · Cited by 30 · see citing works
“Gamma delta (γδ) T cells are a unique class of immune cells, which play important roles in both innate and adaptive cellular immunity [1, 2].”
Background
Standardized and flexible eight colour flow cytometry panels harmonized between different laboratories to study human NK cell phenotype and function
Veluchamy, J. P., Delso-Vallejo, M., Kok, N., Bohme, F., Seggewiß-Bernhardt, R., van der Vliet, H. J., de Gruijl, T. D., Huppert, V., & Spanholtz, J. (2017) · Scientific Reports · doi:10.1038/srep43873 · Cited by 29 · see citing works
Distinct phenotype and function of circulating Vδ1+ and Vδ2+ γδT-cells in acute and chronic hepatitis B
Chang, K., Traum, D., Park, J., Ho, S., Ojiro, K., Wong, D., Wahed, A. S., Terrault, N. A., Khalili, M., Sterling, R. K., et al. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007715 · Cited by 28 · see citing works
Transcriptomic signature of gut microbiome-contacting cells in colon of spontaneously hypertensive rats
Yang, T., Li, H., Oliveira, A. C. D. S., Goel, R., Richards, E. M., Pepine, C. J., & Raizada, M. K. (2019) · Physiological Genomics · doi:10.1152/physiolgenomics.00087.2019 · Cited by 28 · see citing works
Understanding human γδ T cell biology toward a better management of cytomegalovirus infection
Kaminski, H., Marsères, G., Cosentino, A., Guerville, F., Pitard, V., Fournié, J., Merville, P., Déchanet‐Merville, J., & Couzi, L. (2020) · Immunological Reviews · doi:10.1111/imr.12922 · Cited by 27 · see citing works
Ontogenic timing, T cell receptor signal strength, and Notch signaling direct γδ T cell functional differentiation in vivo
Chen, E. L. Y., Lee, C. R., Thompson, P. K., Wiest, D. L., Anderson, M. K., & Zúñiga‐Pflücker, J. C. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109227 · Cited by 27 · see citing works
“These results suggest that either strength of TCR signaling is permissive for γδ T1 differentiation (Jensen et al., 2008; Ribeiro et al., 2015).”
Phenotypic Changes and Impaired Function of Peripheral γδ T Cells in Patients With Sepsis
Liao, X.-L., Feng, T., Zhang, J.-Q., Cao, X., Wu, Q., Xie, Z., Kang, Y., & Li, H. (2017) · Shock · doi:10.1097/shk.0000000000000857 · Cited by 27 · see citing works
Glutaminolysis Mediated by MALT1 Protease Activity Facilitates PD-L1 Expression on ABC-DLBCL Cells and Contributes to Their Immune Evasion
Xia, X., Zhou, W., Guo, C., et al. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00632 · Cited by 27 · see citing works
γδ T cells cultured with artificial antigen-presenting cells and IL-2 show long-term proliferation and enhanced effector functions compared with γδ T cells cultured with only IL-2 after stimulation with zoledronic acid
Choi, H., Lee, Y., Hur, G., et al. (2021) · Cytotherapy · doi:10.1016/j.jcyt.2021.06.002 · Cited by 24 · see citing works
Large Scale Ex Vivo Expansion of γδ T cells Using Artificial Antigen-presenting Cells
Boucher, J. C., Yu, B., Li, G., et al. (2022) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000445 · Cited by 23 · see citing works
Corrigendum: IL-12 Expands and Differentiates Human Vγ2Vδ2 T Effector Cells Producing Antimicrobial Cytokines and Inhibiting Intracellular Mycobacterial Growth
Yang, R., Yao, L., Shen, L., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01742 · Cited by 22 · see citing works
Effect of handling and crowding on the susceptibility of Atlantic salmon (Salmo salar L.) to Lepeophtheirus salmonis (Krøyer) copepodids
Delfosse, C., Pageat, P., Lafont‐Lecuelle, C., et al. (2020) · Journal of Fish Diseases · doi:10.1111/jfd.13286 · Cited by 21 · see citing works
Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity
Kathamuthu, G. R., Kumar, N. P., Moideen, K., et al. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.756854 · Cited by 21 · see citing works
“Among them, gd T cells are innate-like T lymphocytes that comprise a small segment (1%–5%) of the circulating T lymphocytes and play a vital role in triggering host cell-mediated immune responses (Hiromatsu et al., 1992; Ribeiro et al., 2015).”
Background
Human allogenic γδ T cells kill patient-derived glioblastoma cells expressing high levels of DNAM-1 ligands
Choi, H., Lee, Y., Park, S. A., et al. (2022) · OncoImmunology · doi:10.1080/2162402x.2022.2138152 · Cited by 21 · see citing works
“transformed cells in a major histocompatibility complexunrestricted manner has been considered an advantage to their use in anti-tumor therapy.(13) Along with the γδ T cell receptor,”
Background
Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption
Siddiqui, S., Lustig, A., Carter, A., Sankar, M., Daimon, C. M., Premont, R. T., Etienne, H., van Gastel, J., Azmi, A., Janssens, J., et al. (2017) · Aging · doi:10.18632/aging.101185 · Cited by 21 · see citing works
“Inspection of the individual transcripts coherently regulated across ILN/MLN/ spleen/thymus in GIT2KO mice demonstrated that, aside from the expected changes in immune-related factors (Btla [79], Tnfrsf4 [80], AI467606 [81]), there were significant reductions in multiple clock-related transcripts that are also associa…”
The Tumor Microenvironment of Hepatocellular Carcinoma: Untying an Intricate Immunological Network
Volponi, C., Gazzillo, A., & Bonavita, E. (2022) · Cancers · doi:10.3390/cancers14246151 · Cited by 19 · see citing works
γδ T Cells in Skin Inflammation
Zhang, W., Pajulas, A., & Kaplan, M. H. (2022) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2022047288 · Cited by 19 · see citing works
Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis
Bhat, S. A., Elnaggar, M. M., Hall, T. J., McHugo, G. P., Reid, C., MacHugh, D. E., & Meade, K. G. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1265038 · Cited by 19 · see citing works
Disrupting the balance between activating and inhibitory receptors of γδT cells for effective cancer immunotherapy
Beringer, D. X., Straetemans, T., Minguet, S., Riillo, C., Lynch, L., Sebestyén, Z., & Kuball, J. H. E. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00830-x · Cited by 18 · see citing works
Structural characterization of two γδ TCR/CD3 complexes
Hoque, M., Grigg, J. B., Ramlall, T. F., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55467-5 · Cited by 17 · see citing works
γδ T Cells: Game Changers in Immune Cell Therapy for Cancer
Subhi‐Issa, N., Manzano, D. T., Rodriguez, A. P., Sánchez‐Ramón, S., Segura, P. P., & Ocaña, A. (2025) · Cancers · doi:10.3390/cancers17071063 · Cited by 17 · see citing works
“Incorporating NKG2D ligands in vitro or using recombinant proteins that engage NKG2D can significantly enhance γδ T cell expansion and functional potency, by amplifying T-cell cytokine production, proliferation, and cytotoxicity in vitro [26,110,111].”
Roles of γδT cells in pregnancy and pregnancy‐related complications
Xu, Q., Liu, H., Wang, L., Zhu, Q., Zhang, Y., Muyayalo, K. P., & Liao, A. (2021) · American Journal of Reproductive Immunology · doi:10.1111/aji.13487 · Cited by 16 · see citing works
Ancient Use of Ig Variable Domains Contributes Significantly to the TCRδ Repertoire
Deiss, T. C., Breaux, B., Ott, J. A., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900369 · Cited by 16 · see citing works
Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the Thymus
Mengrelis, K., Lau, C., Rowell, J., Solanki, A., Norris, S., Ross, S. E., Ono, M., Outram, S. V., & Crompton, T. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01629 · Cited by 15 · see citing works
Casein kinase 2 controls the survival of normal thymic and leukemic γδ T cells via promotion of AKT signaling
Ribeiro, S. T., Tesio, M., Ribot, J. C., et al. (2016) · Leukemia · doi:10.1038/leu.2016.363 · Cited by 16 · see citing works
“CK2 activity was measured in cell lysates (from equal cell numbers) using the Casein Kinase-2 Assay kit (17-132) from Upstate Biotechnology, following the manufacturer’s instructions.”
Self-citation
Transcriptional Memory-Like Imprints and Enhanced Functional Activity in γδ T Cells Following Resolution of Malaria Infection
Kumarasingha, R., Ioannidis, L. J., Abeysekera, W., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.582358 · Cited by 14 · see citing works
Inversed Ratio of CD39/CD73 Expression on γδ T Cells in HIV Versus Healthy Controls Correlates With Immune Activation and Disease Progression
Kolbe, K., Wittner, M., Hartjen, P., Hüfner, A.-D., Degen, O., Ackermann, C., Cords, L., Stellbrink, H., Haag, F., & Wiesch, J. S. Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.867167 · Cited by 13 · see citing works
The Spectrum of CAR Cellular Effectors: Modes of Action in Anti-Tumor Immunity
Nguyen, T., Müller, R., Briukhovetska, D., Weber, J., Feucht, J., Künkele, A., Hudecek, M., & Kobold, S. (2024) · Cancers · doi:10.3390/cancers16142608 · Cited by 13 · see citing works
“The detection of phosphorylated Zap-70, PI3K, LAT, ERK, PKC and MAPK with subsequent release of IFN-γ and TNF-α in activated V δ 2 T cells implies similar pathways to αβ TCR signaling, but does not necessarily verify the exact mechanism [228–230].”
Background
Human gamma-delta (γδ) T cell therapy for glioblastoma: A novel alternative to overcome challenges of adoptive immune cell therapy
Choi, H., Kim, T., Jeun, S., & Ahn, S. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216335 · Cited by 14 · see citing works
CAR-γδ T cells: a new paradigm of programmable innate immune sentinels and their systemic applications in cancer and beyond
Fang, X., Yan, S., He, L., & Deng, C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1735763 · Cited by 12 · see citing works
Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy
Bridge, J. E., Johnson, M. J., Kar, B., Kim, J., Wenthe, S. J., Krueger, J. B., Wick, B. J., Kluesner, M. G., Crane, A. T., Bell, J., et al. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.03.007 · Cited by 11 · see citing works
“T cells can also be activated via TCR-independent mechanisms 6 including natural killer group 2D (NKG2D), a receptor shared by NK, , and CD8+ T cells that binds to MHC class I polypeptide-related sequence-A and -”
Emerging Challenges of Preclinical Models of Anti-tumor Immunotherapeutic Strategies Utilizing Vγ9Vδ2 T Cells
Joalland, N., & Scotet, E. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00992 · Cited by 11 · see citing works
“Importantly, this Self -reactive nature of Vγ9Vδ2 T cells needs to be tightly regulated by a set of various molecules [see (15) and (16), for recent reviews], such as adhesion molecules (i.”
Background
Survival, gene and metabolite responses of Litoria verreauxii alpina frogs to fungal disease chytridiomycosis
Grogan, L. F., Mulvenna, J. P., Gummer, J. P. A., et al. (2018) · Scientific Data · doi:10.1038/sdata.2018.33 · Cited by 11 · see citing works
Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis
Parker, M. E., Mehta, N. U., Liao, T.-C., Tomaszewski, W. H., Snyder, S., Busch, J., & Ciofani, M. (2025) · Nature Immunology · doi:10.1038/s41590-025-02206-7 · Cited by 11 · see citing works
γδ T cells respond directly and selectively to the skin commensal yeast Malassezia for IL-17-dependent fungal control
Ruchti, F., Tuor, M., Mathew, L., McCarthy, N. E., & LeibundGut‐Landmann, S. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1011668 · Cited by 9 · see citing works
Mobilization of γδ T Cells and IL-10 Production at the Acute Phase of Hepatitis E Virus Infection in Cytomegalovirus Carriers
Barragué, H., Fontaine, J., Abravanel, F., et al. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2000187 · Cited by 10 · see citing works
The multisensory regulation of unconventional T cell homeostasis
Darrigues, J., Almeida, V., Conti, E., & Ribot, J. C. (2022) · Seminars in Immunology · doi:10.1016/j.smim.2022.101657 · Cited by 10 · see citing works
Self-citation
The therapeutic role of γδT cells in TNBC
Li, W., Zhao, X., Ren, C., Gao, S., Han, Q., Lu, M. M., & Li, X. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1420107 · Cited by 9 · see citing works
“NKG2D, a C-type lectin receptor, binds ligands that are typically absent in most normal tissues but are overexpressed on tumor cells, thereby enabling gd T cells to recognize and eliminate tumor cells (56).”
Background
The Role of Nuclear Factor-κB in Cancer Immunity and Immunoediting
Mukherjee, S., Pati, S., Dhar, S., Sarkar, T., Paul, S., Basak, U., Chakraborty, S., & Sa, G. (2025) · Cancer Control · doi:10.1177/10732748251406677 · Cited by 9 · see citing works
IL-12 conditioning of peripheral blood mononuclear cells from breast cancer patients promotes the zoledronate-induced expansion of γδ T cells in vitro and enhances their cytotoxic activity and cytokine production
Assy, L., Khalil, S. M., Attia, M., & Salem, M. L. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109402 · Cited by 9 · see citing works
CD28-expressing δ T cells are increased in perivascular adipose tissue of hypertensive mice and in subcutaneous adipose tissue of obese humans
Berillo, O., Comeau, K., Caillon, A., Leclerc, S., Shokoples, B. G., Mahmoud, A., Andelfinger, G., Paradis, P., & Schiffrin, E. L. (2024) · Journal of Hypertension · doi:10.1097/hjh.0000000000003725 · Cited by 9 · see citing works
“Finally, CD28-positive d T-lymphocytes could have a pathogenic role in human hypertension associated with obesity, and could be a potential target for therapy.”
Background
High Activation of γδ T Cells and the γδ2pos T-Cell Subset Is Associated With the Onset of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome, ANRS 12153 CAPRI NK
Pean, P., Nouhin, J., Meng, R., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02018 · Cited by 9 · see citing works
γ9δ2 T-Cell Expansion and Phenotypic Profile Are Reflected in the CDR3δ Repertoire of Healthy Adults
Vyborova, A., Janssen, A., Gatti, L. C. D. E., Karaiskaki, F., Yonika, A., van Dooremalen, S., Sanders, J., Beringer, D. X., Straetemans, T., Sebestyén, Z., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.915366 · Cited by 8 · see citing works
“org 8 generally considered “signal one” (44), on the landscape of the remaining NKRs and thus on the net NKR signal.”
Background
Angiotensin II-Induced Memory γδ T Cells Sensitize Mice to a Mild Hypertensive Stimulus
Comeau, K., Shokoples, B. G., Caillon, A., Paradis, P., & Schiffrin, E. L. (2023) · American Journal of Hypertension · doi:10.1093/ajh/hpad072 · Cited by 9 · see citing works
Transcriptional programming and gene regulation in WC1+ γδ T cell subpopulations
Damani‐Yokota, P., Zhang, F., Gillespie, A., Park, H., Burnside, A., Telfer, J. C., & Baldwin, C. L. (2021) · Molecular Immunology · doi:10.1016/j.molimm.2021.12.016 · Cited by 8 · see citing works
γδ T cells: The potential role in liver disease and implications for cancer immunotherapy
Ren, H., Li, W., Liu, X., & Zhao, N. (2022) · Journal of Leukocyte Biology · doi:10.1002/jlb.5mr0822-733rrr · Cited by 7 · see citing works
“4 In circulating blood and lymphoid organs of healthy individuals, 50–90%of γδTcells present asVγ9Vδ2.(5) Numerous studies have shown that Vγ9Vδ2 T cells have a vital function in antitumor immunity and immune cell therapy.”
Background
TIGIT-expressing zoledronate-specific γδ T cells display enhanced antitumor activity
You, H., Zhu, H., Zhao, Y., et al. (2022) · Journal of Leukocyte Biology · doi:10.1002/jlb.5ma0822-759r · Cited by 7 · see citing works
Axl is a key regulator of intestinal γδ T‐cell homeostasis
Kim, S., Park, M. J., Yee, S., Ji, K.-Y., Lee, E., Nguyen, T., Nguyen, T. H., Jang, J. H., Kim, E., Choi, H., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201901356r · Cited by 7 · see citing works
In the Acute Phase of Trypanosoma cruzi Infection, Liver Lymphoid and Myeloid Cells Display an Ambiguous Phenotype Combining Pro- and Anti-Inflammatory Markers
dos Santos, C. D. L. P., Vacani-Martins, N., Cascabulho, C. M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.868574 · Cited by 6 · see citing works
The Contribution of Human Herpes Viruses to γδ T Cell Mobilisation in Co-Infections
Martini, F., & Champagne, É. (2021) · Viruses · doi:10.3390/v13122372 · Cited by 6 · see citing works
Expression of CD27 and CD28 on γδ T cells from the peripheral blood of patients with allergic rhinitis
Wang, Q., Sun, Q., Chen, Q., Li, H., & Liu, D. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.9354 · Cited by 5 · see citing works
“CD27 and CD28 are two major costimulatory molecules with independent and non‐redundant roles in the activa‐ tion, proliferation and survival of γδ T cells (11,12).”
Background
Streptozotocin (STZ) and schistosomiasis mansoni change the biodistribution of radiopharmaceutical sodium 99m Tc-pertechnetate in mice
Goes, V., Neves, R. H., Arnóbio, A., et al. (2016) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2016.06.003 · Cited by 5 · see citing works
Ligands for Intestinal Intraepithelial T Lymphocytes in Health and Disease
Hada, A., & Xiao, Z. (2025) · Pathogens · doi:10.3390/pathogens14020109 · Cited by 4 · see citing works
Phenotypic characterization of human peripheral γδT‐cell subsets in glioblastoma
Belghali, M. Y., Elmoumou, L., Hazime, R., et al. (2022) · Microbiology and Immunology · doi:10.1111/1348-0421.13016 · Cited by 4 · see citing works
“However, upon activation, γδT cells are known to rapidly upregulate BTLA expression.(7) The engagement of BTLA with its ligand, herpes virus entry mediator, a member of the TNFR family, attenuates γδT cell activation and differentiation.”
Background
BCG vaccination induces antibacterial effector functions among Vδ1/3 T cells that are associated with protection against tuberculosis
Maerz, M. D., Makatsa, M. S., Bucşan, A. N., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102536 · Cited by 3 · see citing works
“41 Therefore, we next sought to assess to what extent the V δ 1/3 T cell repertoire is modulated by IV-BCG.”
Effect of cytokines (IL-2, IL-7, and IL-15) having common γ-chain of receptors on differentiation and maturation of CD4+/CD8+ T-cells in a CD45RA T-lymphocyte population in vitro
Yurova, K. A., Геннадьевна, Х. О., Дунец, Н. А., et al. (2017) · Cell and Tissue Biology · doi:10.1134/s1990519x1705011x · Cited by 3 · see citing works
“High expression of the surface costimulating CD27 molecule, which has its own CD70 ligand on the antigen-presenting cell, is a distinctive feature of naive lymphocytes from more mature T-cell populations (Libregts et al., 2011; van Montfrans et al., 2012; Coquet et al., 2013; Kudryavtsev, 2014; Ribeiro et al., 2015).”
Background
γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans
Chu, T. H., Khairallah, C. F., Shieh, J., et al. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1010103 · Cited by 3 · see citing works
“Given that IL-12 signaling promotes STAT4 phosphorylation and IFNγ production in γδ T cells [29,93] and Yersinia spp.”
Background
Harnessing γδ T Cells as Natural Immune Modulators
Hedges, J. F., & Jutila, M. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-811924-2.00046-8 · Cited by 2 · see citing works
“They also express tumor necrosis factor (TNF) receptor family molecules CD27, CD30, and CD137 [9] .”
Background
Accumulation of γδT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-κB
Chang, R., Dai, J., Qiu, Y.-H., et al. (2024) · Reproduction · doi:10.1530/rep-23-0262 · Cited by 1 · see citing works
A persistent increase in gut permeability correlates with emotional dysregulation following maternal separation in male and female mice
Castro‐Zavala, A., Nieto-Nieves, A. E., Melgar‐Locatelli, S., Medina-Rodríguez, L., Mañas‐Padilla, M. C., & Castilla‐Ortega, E. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115772 · Cited by 1 · see citing works

CD28 and NKG2D-mediated costimulation regulates CD8+ T cell chemotaxis through different signaling pathways
Serrano‐Pertierra, E., Eva, C.-M., & Carlos, L.-L. (2013) · Frontiers in Immunology · doi:10.3389/conf.fimmu.2013.02.00297
NKG2D- and CD28-mediated costimulation regulate CD8+ T cell chemotaxis through different mechanisms: the role of Cdc42/N-WASp
Serrano‐Pertierra, E., Cernuda‐Morollón, E., & López‐Larrea, C. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.0613316 · Cited by 15 · see citing works
Coordinate Regulation of T Cell Activation by CD2 and CD28
Green, J. M., Karpitskiy, V. V., Kimzey, S. L., & Shaw, A. S. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.7.3591 · Cited by 84 · see citing works
Synergy between CD28 and CD9 costimulation for naive T-cell activation
Toyo‐oka, K., Tai, X., Yashiro, Y., Ahn, H., Abe, R., Hamaoka, T., Kobayashi, M., Neben, S., & Fujiwara, H. (1997) · Immunology Letters · doi:10.1016/s0165-2478(97)02706-5 · Cited by 13 · see citing works
CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production
Freeman, G. J., Lombard, D. B., Gimmi, C. D., Brod, S. A., Lee, K., Laning, J. C., Hafler, D. A., Dorf, M. E., Gray, G. S., & Reiser, H. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.149.12.3795 · Cited by 150 · see citing works

Authors: Ribeiro, S. T., Ribot, J. C., & Silva-Santos, B.
Affiliations: University of Lisbon (PT)
ORCID: Ribot, Julie C.
Venue: Frontiers in Immunology
Publisher: Frontiers Media SA
Published: 2015-01-26
Volume: 6
Pages: 15-15
ISSN: 1664-3224 (ISSN-L)
DOI: 10.3389/fimmu.2015.00015
PMC: PMC4306313
OpenAlex: W2027271725
Semantic Scholar: d2d3632814aa56e04fe85192b8fcd093a630672b
Cited by: 116
References: 127
Citations by year: 2026: 5 · 2025: 9 · 2024: 7 · 2023: 4 · 2022: 15 · 2021: 21 · 2020: 15 · 2019: 13 · 2018: 13 · 2017: 8 · 2016: 4 · 2015: 2
FWCI: 0.85
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Immunology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Funders: Fundação para a Ciência e a Tecnologia (SFRH/BD/84123/2012)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords: γδ T cells, receptor signaling, T cell activation, T cell differentiation, costimulatory receptors, CD27, CD28, cytokine receptors, interleukin-2 receptor, IL-7 receptor, IL-15 receptor, NK cell receptors, NKG2D, cytotoxicity, inhibitory receptors, PD-1, BTLA, T cell homeostasis, immunotherapy

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Five Layers of Receptor Signaling in Î³Î´ T-Cell Differentiation and Activation

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