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Tissue-Resident Memory T Cells
Open accessAbstract
Tissue-resident memory T (Trm) cells constitute a recently identified lymphocyte lineage that occupies tissues without recirculating. They provide a first response against infections reencountered at body surfaces, where they accelerate pathogen clearance. Because Trm cells are not present within peripheral blood, they have not yet been well characterized, but are transcriptionally, phenotypically, and functionally distinct from recirculating central and effector memory T cells. In this review, we will summarize current knowledge of Trm cell ontogeny, regulation, maintenance, and function and will highlight technical considerations for studying this population.
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“These Trm are specially programmed to persist in their host tissues [249, 250].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [249]
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“residency molecules, such as CD103 and CD69, and maintain the ability to produce effector molecules such as granzyme B (GzmB), TNF, IFN-γ, and IL-2 depending on their site of residence [5].”
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“9), CD14 (M5E2), CD16 (3G8), CD24 (ML5), CD45 (HI30), CD45RA (HI100), CD56 (HCD56), CD123 (6H6), CD169 (7-239), and CD206 (15-2), purchased from BioLegend (San Diego, CA); CD45RO (UCHL1), T-bet (eBio4B10), and HLA-DR (LN3), purchased from eBioscience/Thermo Fisher (San Jose, CA); and CD8 (SK1), CD69 (FN50), and CD103…”
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TGF-β-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine
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Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection
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Peripheral tissue chemokines: homeostatic control of immune surveillance T cells.
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“Human skin CCR8 T cells bear many of the hallmarks ascribed to mouse TRM cells [7-10], including CD69/CD103 expression, proliferation responses to steady-state growth factors IL-7 and IL-15 and lower expression of Eomes and T-bet.”
BackgroundThe use of cell-mediated immunity for the evaluation of influenza vaccines: an upcoming necessity
Gianchecchi, E., Torelli, A., & Montomoli, E. (2019) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2019.1565269 · Cited by 42
Emerging Concepts of Tissue-resident Memory T Cells in Transplantation
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Chemokine Receptor-Targeted Therapies: Special Case for CCR8
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The cellular and molecular basis of CD69 function in anti-tumor immunity
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Mockus, T. E., Shwetank, Lauver, M. D., Ren, H. M., Netherby, C. S., Salameh, T. J., Kawasawa, Y. I., Yue, F., Broach, J. R., & Lukacher, A. E. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007365 · Cited by 41
“These findings support accumulating evidence that caution is warranted when considering CD103 as a stereotypical marker of T RM differentiation [1, 36] .”
BackgroundInfluentialWoodworth, J. S., Christensen, D., Cassidy, J. P., Agger, E. M., Mortensen, R. J., & Andersen, P. L. (2019) · Mucosal Immunology · doi:10.1038/s41385-019-0145-5 · Cited by 41
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Ryba-Stanisławowska, M. E., Sakowska, J., Zieliński, M., Ławrynowicz, U., & Trzonkowski, P. (2019) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2019.1620602 · Cited by 38
“nodes as central memory T cells or in peripheral tissues as tissueresidentmemory T cells [30,31].”
BackgroundPaterson, S., Kar, S., Ung, S. K. A., Gardener, Z., Bergstrom, E., Ascough, S., Kalyan, M., Żyła, J., Maertzdorf, J., Mollenkopf, H., et al. (2021) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202103-0620oc · Cited by 36
“Resident memory T (Trm) cells are a tissue-restricted memory subset, poised at sites of potential infection to prevent disease through rapid responses to antigen reexposure (7).”
BackgroundPascutti, M. F., Geerman, S., Collins, N., Brasser, G., Nota, B., Stark, R., Behr, F., Oja, A., Slot, E., Panagioti, E., et al. (2019) · European Journal of Immunology · doi:10.1002/eji.201848003 · Cited by 37
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Lucas, E. D., Huggins, M. A., Peng, C., O’Connor, C., Gress, A. R., Thefaine, C. E., Dehm, E. M., Kubota, Y., Jameson, S. C., & Hamilton, S. E. (2024) · Science Immunology · doi:10.1126/sciimmunol.adj8356 · Cited by 39
“In stark contrast to LLECs, TRM cells seed lymphoid and nonlymphoid organs during primary infection and do not reenter the circulation ( 13 ).”
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“(1-4) Because TRM cells occupy the front-line sites of infection, they are able to immediately respond to the invasion of pathogens.(5) In contrast, TRM cells have also been implicated in the pathogenesis of various skin diseases, such as psoriasis and vitiligo,(6) and targeting TRM cells has been proposed to reduce t…”
BackgroundFuel and brake of memory T cell inflation
Welten, S. P. M., Baumann, N. S., & Oxenius, A. (2019) · Medical Microbiology and Immunology · doi:10.1007/s00430-019-00587-9 · Cited by 36
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Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells
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“Tissueresident T cells can have significant differences in responses including gene expression, proliferation, and motility (52).”
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Joseph, E. L. M., Kirilovsky, A., Lecoester, B., Sissy, C. E., Boullerot, L., Rangan, L., Marguier, A., Tochet, F., Dosset, M., Boustani, J., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002256 · Cited by 42
Varese, A., Nakawesi, J., Farias, A., Kirsebom, F. C. M., Paulsen, M., Nuriev, R. I., & Johansson, C. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010272 · Cited by 36
“In addition, in the lungs of humans and mice, TRM cells can also express integrin α1 sub-unit (CD49a) and CCL16 chemokine receptor CXCR6[8–10] but are heterogeneous and exhibit different expression levels of other surface markers [11,12].”
BackgroundEfficiency of Chitosan Nanocarriers in Vaccinology for Mucosal Immunization
Gaglio, S. C., Perduca, M., Zipeto, D., & Bardi, G. (2023) · Vaccines · doi:10.3390/vaccines11081333 · Cited by 41
SOX2 immunity and tissue resident memory in children and young adults with glioma
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Regulation of tissue-resident memory T cells by the Microbiota
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Recent advances in respiratory immunization: A focus on COVID-19 vaccines
He, X., Chen, X., Wang, H., Du, G., & Sun, X. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.02.011 · Cited by 37
Virtual memory T cells orchestrate extralymphoid responses conducive to resident memory
Hou, S., Shao, T., Mao, T., Shi, J., Sun, J., Mei, M., Tan, X., & Qi, H. (2021) · Science Immunology · doi:10.1126/sciimmunol.abg9433 · Cited by 36
“The rapid recruitment and early tissue entrapment probably subject antigen-specific TVM cells to prolonged exposure to residence-inducing factors such as transforming growth factor– (TGF-) (41, 42), thus favoring TRM development.”
BackgroundInfluentialZheng, C., Cao, T., Ye, C., & Zou, Y. (2023) · Clinical Immunology · doi:10.1016/j.clim.2023.109805 · Cited by 35
Scholzen, A., & Sauerwein, R. W. (2016) · Parasitology · doi:10.1017/s0031182015000761 · Cited by 36
Fresnay, S., McArthur, M. A., Magder, L. S., Darton, T. C., Jones, C., Waddington, C. S., Blohmke, C. J., Angus, B., Levine, M. M., Pollard, A. J., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00208 · Cited by 34
Morabito, K. M., Ruckwardt, T. J., Bar‐Haim, E., Nair, D., Moin, S. M., REDWOOD, A. J., Price, D. A., & Graham, B. S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01861 · Cited by 35
Bull, N. C., Kaveh, D. A., García‐Pelayo, M. C., Stylianou, E., McShane, H., & Hogarth, P. J. (2018) · Vaccine · doi:10.1016/j.vaccine.2018.07.035 · Cited by 38
Haddadi, S., Vaseghi‐Shanjani, M., Yao, Y., Afkhami, S., D’Agostino, M. R., Zganiacz, A., Jeyanathan, M., & Xing, Z. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02075 · Cited by 35
“Ag85A tetramer (Ag)-specific CD8T cells (CD44+CD62L-tet+) and their TRM phenotype (coexpression of CD103 and CD69 or CD49a and CD69) (16, 27) were examined in the airway (BAL) and lung parenchymal tissue (LPT).”
BackgroundMatyushenko, V., Kotomina, T. S., Kudryavtsev, I. V., Mezhenskaya, D. А., Prokopenko, P., Matushkina, A., Сивак, К. В., Muzhikyan, A., Георгиевна, Р. Л., & Isakova–Sivak, I. (2020) · Antiviral Research · doi:10.1016/j.antiviral.2020.104864 · Cited by 35
T Cell Immunity and the Quest for Protective Vaccines against Staphylococcus aureus Infection
Armentrout, E. I., Liu, G. E., & Martins, G. A. (2020) · Microorganisms · doi:10.3390/microorganisms8121936 · Cited by 36
“Studies using different infection models [95–97], indicate that TRM cells develop from memory precursors that enter the tissue during the effector phase of infection and remain in the tissue afterwards [98].”
MethodTissue Resident Foxp3+ Regulatory T Cells: Sentinels and Saboteurs in Health and Disease
Lee, J., Kim, D., & Min, B. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.865593 · Cited by 38
“They are also found to display transcriptionally distinct programs from those of circulating memory counterparts, suggesting a distinct mechanism for their homeostasis and functions (22, 23).”
BackgroundA lymphocyte chemoaffinity axis for lung, non-intestinal mucosae and CNS
Ocón, B., Xiang, M., Bi, Y., Tan, S. Y., Brulois, K., Ayesha, A., Kunte, M., Zhou, C., LaJevic, M. D., Lazarus, N. H., et al. (2024) · Nature · doi:10.1038/s41586-024-08043-2 · Cited by 39
Feng, R., Spieth, L., Liu, L., Berghoff, S. A., Franz, J., Liu, Q., Wang, Z., Tiwari, V., Vitale, S., Frerich, S., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.10.003 · Cited by 40
“13,14 However, they have also been linked to the development of several autoimmune diseases.”
Resident Memory T Cells as Surrogate Markers of the Efficacy of Cancer Vaccines
Nizard, M., Roussel, H., & Tartour, É. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2364 · Cited by 35
Memory CD8(+) T Cells: Innate-Like Sensors and Orchestrators of Protection
Lauvau, G., Boutet, M., Williams, T. M., Chin, S. S., & Chorro, L. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.04.001 · Cited by 35
Tissue-Resident Lymphocytes in Solid Organ Transplantation
Prosser, A., Kallies, A., & Lucas, M. (2017) · Transplantation · doi:10.1097/tp.0000000000002001 · Cited by 36
The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+ T cells
Moalli, F., Ficht, X., Germann, P., Vladymyrov, M., Stolp, B., de Vries, I., Lyck, R., Balmer, J., Fiocchi, A., Kreutzfeldt, M., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20170896 · Cited by 35
“Finally, our data are consistent with a scenario where epithelial BM serves as a physical barrier to contain transmigrated effector T cells in NLT niches and allow them to become TRM through changes in expression of transcription factors, chemoattractant receptors, and integrins (Mueller et al., 2013; Schenkel and Mas…”
BackgroundResultGenealogy, Dendritic Cell Priming, and Differentiation of Tissue-Resident Memory CD8+ T Cells
Enamorado, M., Khouili, S. C., Iborra, S., & Sancho, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01751 · Cited by 37
David, S. C., Norton, T. S., Tyllis, T. S., Wilson, J. J., Singleton, E. V., Laan, Z., Davies, J. B., Hirst, T. R., Comerford, I., McColl, S. R., et al. (2019) · Nature Microbiology · doi:10.1038/s41564-019-0443-4 · Cited by 34
Inflammation and immunity in ovarian cancer
Salas‐Benito, D., Vercher, E., Conde, E., Glez‐Vaz, J., Tamayo, I., & Hervás‐Stubbs, S. (2020) · European Journal of Cancer Supplements · doi:10.1016/j.ejcsup.2019.12.002 · Cited by 35
“CD103 is also expressed by intraepithelial lymphocytes and tissue-resident memory (TRM) cells, important mediators of adaptive immunity in peripheral tissues [40,41].”
BackgroundRice, S. A. (2021) · Viruses · doi:10.3390/v13122395 · Cited by 34
“TRMs are a subset of CD8+ T cells that are permanently localized to specific tissues and serve as first responders to fight off reinfections at body surfaces [104].”
BackgroundTissue-Resident Memory CD4+ T Cells Play a Dominant Role in the Initiation of Antitumor Immunity
Zhang, H., Zhu, Z., Modrak, S., & Little, A. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2100852 · Cited by 34
An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission
Adler, J. M., Vidal, R. M., Langner, C., Vladimirova, D., Abdelgawad, A., Kunecova, D., Lin, X., Nouailles, G., Voß, A., Kunder, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45348-2 · Cited by 36
“…repertoire at the respiratory mucosa, which among other things, triggers the formation of tissue-resident memory T cells (TRM cells), a specialized subset of T cells that remain stationary in speci fi c tissues, such as the respiratory mucosa, after an initial infection or vaccination 39,40 .”
Mucosal vaccine development for respiratory viral infections
Lin, Y., Hu, Z., Fu, Y., & Peng, H. (2023) · hLife · doi:10.1016/j.hlife.2023.12.005 · Cited by 33
Maintenance of pathogenic Th2 cells in allergic disorders
Shinoda, K., Hirahara, K., & Nakayama, T. (2017) · Allergology International · doi:10.1016/j.alit.2017.03.005 · Cited by 33
Past Life and Future Effects—How Heterologous Infections Alter Immunity to Influenza Viruses
Souquette, A. H., & Thomas, P. G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01071 · Cited by 34
Schiffer, J. T., Swan, D. A., Prlic, M., & Lund, J. M. (2018) · Immunological Reviews · doi:10.1111/imr.12672 · Cited by 32
Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and antitumor immunity
Medina, B. D., Liu, M., Vitiello, G. A., Seifert, A. M., Zeng, S., Bowler, T. G., Zhang, J. Q., Cavnar, M. J., Loo, J. K., Param, N. J., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20180660 · Cited by 34
“This is consistent with the proposed function of resident memory T cells as a noncirculating subset specialized in rapid response to immunological challenge (Schenkel and Masopust, 2014).”
Zhao, Q., Kong, L.-Y., Jiang, S., Tian, X., Wang, J., Hashizume, R., Hu, J., Jia, Z., Fowlkes, N. W., Yan, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36430-2 · Cited by 33
Self-citationWhat Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans?Preprint
Jameson, S. C., & Masopust, D. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a029132 · Cited by 33
Self-citationMauro, D., Lin, X., Pontarini, E., Wehr, P., Guggino, G., Tang, Y., Deng, C., Gandolfo, S., Xiao, F., Rui, K., et al. (2024) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2023-225069 · Cited by 32
Veytia‐Bucheli, J. I., Jiménez-Vargas, J. M., Melchy-Pérez, E., Sandoval-Hernández, M. A., Possani, L. D., & Rosenstein, Y. (2018) · Cell Communication and Signaling · doi:10.1186/s12964-018-0257-7 · Cited by 32
Metadata
- Authors
- Schenkel, J. M., & Masopust, D.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Masopust, David
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 41
- Issue
- 6
- Pages
- 886-897
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4276131
- OpenAlex
- W2046700010
- Cited by
- 1,059
- References
- 135
- Citations by year
- 2026: 74 · 2025: 84 · 2024: 88 · 2023: 92 · 2022: 108 · 2021: 113 · 2020: 103 · 2019: 102 · 2018: 96 · 2017: 81 · 2016: 71 · 2015: 45 · 2014: 1
- FWCI
- 6.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI084913, R01AI111671, R37AI084913, T32AI007313)
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK100159)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- tissue-resident memory T cells, mucosal immunity, memory T cell differentiation
- MeSH terms
- Animals, Cell Differentiation, Cell Movement, Humans, Immunity, Immunologic Memory, T-Lymphocytes, T-Lymphocyte Subsets
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