CD4 CTL, a cytotoxic subset of CD4(+) T cells, their differentiation and function
Open accessAbstract
CD4+ T cells with cytotoxic activity (CD4 CTL) have been observed in a variety of immune responses. These cells are characterized by their ability to secrete granzyme B and perforin, and to kill the target cells in an MHC class II-restricted fashion. Although CD4 CTLs were once thought to be an in vitro artifact associated with long term culturing, they have since been identified in vivo and shown to play important roles in antiviral and antitumor immunity, as well as in inflammation. Functional characterization of CD4 CTL suggests their potential significance for therapeutic purposes. However, in order to develop effective CD4 CTL therapy it is necessary to understand the differentiation and generation of these cells. Although the mechanisms regulating development of various CD4+ Th subsets have been clarified in terms of the cytokine and transcription factor requirement, the CD4 CTL differentiation mechanism remains elusive. These cells are thought to be most closely related to Th1 cells secreting IFNγ, and regulated by Eomesodermin (Eomes) and/or T-bet transcription factors for their differentiation. However, our studies and those of others have identified CD4 CTLs within other CD4+ T cell subsets, including naïve T cells. We have identified CRTAM as a marker of CD4 CTL and, by using this marker, we detected a subset of naïve T cells that have the potential to differentiate into CD4 CTL. CD4 CTL develop at sites of infections as well as inflammation. In this review, we summarize recent findings about the generation of CD4 CTL, and propose a model with several differentiation pathways.
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In post-cryoablated RMS 76-9STINGwt TME compared with RMS 76-9STING-/- TME in wild-type mice, there was a significant increase in total CD4+ T cells expressing IFN-γ and GZMB, NK cells, GZMB expression in CD8+ T cells, and Foxp3+ CD4+ cells.
“we observed a significant increase in the total CD4+ T cells expressing IFN-γ (figure 4H) and granzyme B (GZMB; figure 4J),60–65 NK cells (figure 4N), and the amount of GZMB expression in CD8+ T cells (figure 4L) in the post-cryoablated RMS 76-9STINGwt TME as compared with RMS 76-9STING-/- TME in wild-type mice, as was Foxp3+ CD4+ cells (figure 4M).”
From Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation (2023) · cites this paper as [65]
The Introduction says cytotoxic CD4+ T cells can contain granzyme B, and the Differentiation of CD4 CTL section discusses IFN-γ production. Neither section reports the cited increase after cryoablation, the RMS 76-9 STING comparison, or the NK, CD8+, and Foxp3+ findings; those are presented in the citing sentence as its authors’ own observations. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCD4 CTL recognizes target cells via peptide-MHC II complex on APCs.
“CD4 CTL recognizes target cells via peptide-MHC II complex on APCs (53).”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [53]
CD4+ CTLs are characterized by their cytotoxic functions to secrete granzyme B and perforin, two major tools to directly kill the target cells.
“CD4+ CTLs are characterized by their cytotoxic functions to secrete granzyme B and perforin, two major tools to directly kill the target cells.”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [53]
CD4+ T cells also contribute to direct tumor killing besides their supporting role as cytokine producers.
“Although CD8+ T cells are known to play a pivotal role in antitumor immunity, CD4+ T cells also contribute to direct tumor killing besides their supporting role as cytokine producers.”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [53]
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Cites
Mosmann, T. R., Cherwinski, H. M., Bond, M. W., Giedlin, M. A., & Coffman, R. L. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.7.2348 · Cited by 7,438 · see citing works
Up on the tightrope: natural killer cell activation and inhibition
Lanier, L. L. (2008) · Nature Immunology · doi:10.1038/ni1581 · Cited by 1,656 · see citing works
Control of Effector CD8 <sup>+</sup> T Cell Function by the Transcription Factor <i>Eomesodermin</i>
Pearce, E. L., Mullen, A. C., Martins, G. A., Krawczyk, C. M., Hutchins, A. S., Zediak, V. P., Banica, M., DiCioccio, C. B., Gross, D. A., Mao, C.-A., et al. (2003) · Science · doi:10.1126/science.1090148 · Cited by 1,014 · see citing works
Expanding roles for CD4+ T cells in immunity to viruses
Swain, S. L., McKinstry, K. K., & Strutt, T. M. (2012) · Nature reviews. Immunology · doi:10.1038/nri3152 · Cited by 960 · see citing works
Quezada, S. A., Simpson, T. R., Peggs, K. S., Merghoub, T., Vider, J., Fan, X., Blasberg, R., Yagita, H., Muranski, P., Antony, P. A., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091918 · Cited by 898 · see citing works
Endogenous MHC Class II Processing of a Viral Nuclear Antigen After Autophagy
Paludan, C., Schmid, D., Landthaler, M., Vockerodt, M., Kube, D., Tuschl, T., & Münz, C. (2005) · Science · doi:10.1126/science.1104904 · Cited by 860 · cited 2× · see citing works
“These peptides are typically derived from outside the cell as exogenous Ags, but endogenous self-peptides can also be presented through the autophagy process (21, 22).”
BackgroundPipkin, M. E., Sacks, J. A., Cruz‐Guilloty, F., Lichtenheld, M. G., Bevan, M. J., & Rao, A. (2010) · Immunity · doi:10.1016/j.immuni.2009.11.012 · Cited by 799 · see citing works
Borrego, F., Ulbrecht, M., Weiss, E. H., Coligan, J. E., & Brööks, A. G. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.5.813 · Cited by 726 · see citing works
Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes.
Peters, P. J., Borst, J. G., Oorschot, V. M. J., Fukuda, M., Krähenbühl, O., Tschopp, J. F., Slot, J. W., & Geuze, H. J. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.5.1099 · Cited by 713 · see citing works
Autophagy promotes MHC class II presentation of peptides from intracellular source proteins
Dengjel, J., Schoor, O., Fischer, R., Reich, M. R., Kraus, M., Müller, M., Kreymborg, K., Altenberend, F., Brandenburg, J., Kalbacher, H., et al. (2005) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0501190102 · Cited by 680 · see citing works
Levitskaya, J., Sharipo, A., Leonchiks, A., Ciechanover, A. J., & Masucci, M. G. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12616 · Cited by 562 · see citing works
Characterization of CD4+ CTLs Ex Vivo
Appay, V., Zaunders, J. J., Papagno, L., Sutton, J., Jaramillo, A., Waters, A., Easterbrook, P., Grey, P., Smith, D. E., McMichael, A. J., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5954 · Cited by 545 · see citing works
Vance, R. E., Leavey, J. K., Altman, J. D., Jensen, P. E., & Raulet, D. H. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.10.1841 · Cited by 482 · see citing works
Naive tumor-specific CD4+ T cells differentiated in vivo eradicate established melanoma
Xie, Y., Akpınarlı, A., Maris, C. H., Hipkiss, E. L., Lane, M. V., Kwon, E. M., Muranski, P. J., Restifo, N. P., & Antony, P. A. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20091921 · Cited by 455 · see citing works
TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer
Kuramochi, M., Fukuhara, H., Nobukuni, T., Kanbe, T., Maruyama, T., Ghosh, H. P., Pletcher, M. T., Isomura, M., Onizuka, M., Kitamura, T., et al. (2001) · Nature Genetics · doi:10.1038/86934 · Cited by 441 · see citing works
Mucida, D., Husain, M. M., Muroi, S., van Wijk, F., Shinnakasu, R., Naoe, Y., Reis, B. S., Huang, Y., Lambolez, F., Docherty, M., et al. (2013) · Nature Immunology · doi:10.1038/ni.2523 · Cited by 376 · see citing works
van Leeuwen, E. M. M., Remmerswaal, E. B. M., Vossen, M. T. M., Rowshani, A. T., Dillen, P. M. E. W., van Lier, R. A. W., & ten Berge, I. J. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.1834 · Cited by 369 · see citing works
Casazza, J. P., Betts, M. R., Price, D. A., Precopio, M., Ruff, L. E., Brenchley, J. M., Hill, B. J., Roederer, M., Douek, D. C., & Koup, R. A. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052246 · Cited by 338 · see citing works
Recent developments in the transcriptional regulation of cytolytic effector cells
Glimcher, L. H., Townsend, M. J., Sullivan, B. M., & Lord, G. M. (2004) · Nature reviews. Immunology · doi:10.1038/nri1490 · Cited by 293 · see citing works
Reis, B. S., Rogoz, A., Costa‐Pinto, F. A., Taniuchi, I., & Mucida, D. (2013) · Nature Immunology · doi:10.1038/ni.2518 · Cited by 275 · see citing works
Sujino, T., London, M., Hoytema van Konijnenburg, D. P., Rendon, T., Buch, T., Silva, H. M., Lafaille, J. J., Reis, B. S., & Mucida, D. (2016) · Science · doi:10.1126/science.aaf3892 · Cited by 250 · see citing works
T-Cell-Receptor-Dependent Signal Intensity Dominantly Controls CD4+ T Cell Polarization In Vivo
van Panhuys, N., Klauschen, F., & Germain, R. N. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.003 · Cited by 246 · see citing works
Brown, D. M., Lee, S., García-Hernández, M. D. L. L., & Swain, S. L. (2012) · Journal of Virology · doi:10.1128/jvi.07172-11 · Cited by 245 · see citing works
Regulation of CD27 expression on subsets of mature T-lymphocytes.
Hintzen, R. Q., de Jong, R., Lens, S. M. A., Brouwer, M. C., Baars, P. A., & van Lier, R. A. W. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.5.2426 · Cited by 241 · see citing works
CD94-NKG2A receptors regulate antiviral CD8+ T cell responses
Moser, J. M., Gibbs, J. S., Jensen, P. E., & Lukacher, A. E. (2002) · Nature Immunology · doi:10.1038/ni757 · Cited by 220 · see citing works
CRTAM determines the CD4+ cytotoxic T lymphocyte lineage
Takeuchi, A., Badr, M. E. S. G., Miyauchi, K., Ishihara, C., Onishi, R. M., Guo, Z., Sasaki, Y., Ike, H., Takumi, A., Tsuji, N. M., et al. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20150519 · Cited by 210 · see citing works
Self-citationThewissen, M. M., Somers, V. A., Hellings, N., Fraussen, J., Damoiseaux, J. G. M. C., & Stinissen, P. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.10.6514 · Cited by 199 · see citing works
Galibert, L., Diemer, G. S., Liu, Z., Johnson, R. S., Smith, J. L., Walzer, T., Comeau, M. R., Rauch, C. T., Wolfson, M. F., Sorensen, R. A., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502095200 · Cited by 189 · see citing works
Zaunders, J. J. (2003) · Blood · doi:10.1182/blood-2003-08-2765 · Cited by 187 · see citing works
Cytotoxic CD4 T Cells in Antiviral Immunity
Marshall, N. B., & Swain, S. L. (2011) · BioMed Research International · doi:10.1155/2011/954602 · Cited by 184 · see citing works
Cytolytic CD4 cells: Direct mediators in infectious disease and malignancy
Brown, D. M. (2010) · Cellular Immunology · doi:10.1016/j.cellimm.2010.02.008 · Cited by 168 · see citing works
Targeting the MHC Class II antigen presentation pathway in cancer immunotherapy
Thibodeau, J., Bourgeois-Daigneault, M., & Lapointe, R. (2012) · Oncoimmunology · doi:10.4161/onci.21205 · Cited by 167 · see citing works
Brien, J. D., Uhrlaub, J. L., & Nikolich‐Žugich, J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.12.8568 · Cited by 159 · see citing works
Qui, H. Z., Hagymasi, A. T., Bandyopadhyay, S., Rose, M. S., Ramanarasimhaiah, R., Ménoret, A., Mittler, R. S., Gordon, S. M., Reiner, S. L., Vella, A. T., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101244 · Cited by 158 · see citing works
Hirschhorn-Cymerman, D., Budhu, S., Kitano, S., Liu, C., Zhao, F., Zhong, H., Lesokhin, A. M., Avogadri-Connors, F., Yuan, J. D., Li, Y., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20120532 · Cited by 157 · see citing works
Cytotoxic CD4 + T cells in viral hepatitis
Aslan, N., Yurdaydın, C., Wiegand, J., Greten, T. F., Ciner, A., Meyer, M., Heiken, H., Kuhlmann, B., Kaiser, T., Bozkaya, H., et al. (2006) · Journal of Viral Hepatitis · doi:10.1111/j.1365-2893.2006.00723.x · Cited by 153 · see citing works
Regulation of a Late Phase of T Cell Polarity and Effector Functions by Crtam
Yeh, J.-H., Sidhu, S. S., & Chan, A. C. (2008) · Cell · doi:10.1016/j.cell.2008.01.013 · Cited by 139 · see citing works
Yasukawa, M., Ohminami, H., Arai, J. A., et al. (2000) · Blood · doi:10.1182/blood.v95.7.2352 · Cited by 137 · see citing works
CD28 Negative T Cells: Is Their Loss Our Gain?
Mou, D., Espinosa, J. R., Lo, D. J., & Kirk, A. D. (2014) · American Journal of Transplantation · doi:10.1111/ajt.12937 · Cited by 137 · see citing works
Eomesodermin-expressing T-helper cells are essential for chronic neuroinflammation
Raveney, B. J. E., Oki, S., Hohjoh, H., Nakamura, M., Sato, W., Murata, M., & Yamamura, T. (2015) · Nature Communications · doi:10.1038/ncomms9437 · Cited by 130 · see citing works
van de Berg, P. J., van Leeuwen, E. M. M., ten Berge, I. J. M., & van Lier, R. A. W. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.03.007 · Cited by 129 · see citing works
Transcription Factor T-bet Regulates Intraepithelial Lymphocyte Functional Maturation
Reis, B. S., van Konijnenburg, D. P. H., Grivennikov, S. I., & Mucida, D. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.017 · Cited by 129 · see citing works
Brown, D. M., Kamperschroer, C., Dilzer, A. M., Roberts, D. M., & Swain, S. L. (2009) · Cellular Immunology · doi:10.1016/j.cellimm.2009.03.002 · Cited by 125 · see citing works
Thelemann, C., Eren, R. O., Coutaz, M., Brasseit, J., Bouzourène, H., Rosa, M., Duval, A., Lavanchy, C., Mack, V., Mueller, C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086844 · Cited by 122 · see citing works
Lukacher, A. E., Morrison, L. A., Braciale, V. L., et al. (1985) · The Journal of Experimental Medicine · doi:10.1084/jem.162.1.171 · Cited by 121 · see citing works
CD4 CTL: Living up to the challenge
Cheroutre, H., & Husain, M. M. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.10.022 · Cited by 119 · see citing works
Wagner, H., Götze, D., Ptschelinzew, L., et al. (1975) · The Journal of Experimental Medicine · doi:10.1084/jem.142.6.1477 · Cited by 119 · see citing works
Primary type II alveolar epithelial cells present microbial antigens to antigen-specific CD4+T cells
Debbabi, H., Ghosh, S., Kamath, A. B., Alt, J., deMello, D. E., Dunsmore, S. E., & Behar, S. M. (2005) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00004.2005 · Cited by 111 · see citing works
A comparison of viral immune escape strategies targeting the MHC class I assembly pathway
Früh, K., Gruhler, A., Krishna, R. M., & Schoenhals, G. J. (1999) · Immunological Reviews · doi:10.1111/j.1600-065x.1999.tb01290.x · Cited by 108 · see citing works
Lancki, D. W., Hsieh, C., & Fitch, F. W. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.9.3242 · Cited by 107 · see citing works
Expression and function of NKG2D in CD4 + T cells specific for human cytomegalovirus
Sáez‐Borderías, A., Gumá, M., Angulo, A., Bellosillo, B., Pende, D., & López‐Botet, M. (2006) · European Journal of Immunology · doi:10.1002/eji.200636682 · Cited by 107 · see citing works
Zhou, X., & McElhaney, J. E. (2011) · Vaccine · doi:10.1016/j.vaccine.2010.12.029 · Cited by 106 · see citing works
Arase, N., Takeuchi, A., Unno, M., et al. (2005) · International Immunology · doi:10.1093/intimm/dxh299 · Cited by 84 · see citing works
Self-citationHLA-D region-associated determinants serve as targets for human cell-mediated lysis.
Feighery, C., & Stastny, P. (1979) · The Journal of Experimental Medicine · doi:10.1084/jem.149.2.485 · Cited by 79 · see citing works
CRTAM Confers Late-Stage Activation of CD8+ T Cells to Regulate Retention within Lymph Node
Takeuchi, A., Itoh, Y., Takumi, A., Ishihara, C., Arase, N., Yokosuka, T., Koseki, H., Yamasaki, S., Takai, Y., Miyoshi, J., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901248 · Cited by 73 · see citing works
Self-citationHaigh, T. A., Lin, X., Jia, H., Hui, E. P., Chan, A. T. �., Rickinson, A. B., & Taylor, G. S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.3.1643 · Cited by 71 · see citing works
The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection
Brown, D. M., Lampe, A. T., & Workman, A. M. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00093 · Cited by 66 · see citing works
Cortez, V. S., Cervantes‐Barragán, L., Song, C., Gilfillan, S., McDonald, K. G., Tussiwand, R., Edelson, B. T., Murakami, Y., MURPHY, K. M. M., Newberry, R. D., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20130904 · Cited by 57 · see citing works
Donnarumma, T., Young, G. R., Merkenschlager, J., Eksmond, U., Bongard, N., Nutt, S. L., Boyer, C., Dittmer, U., Le‐Trilling, V. T. K., Trilling, M., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.013 · Cited by 57 · see citing works
Billings, P. R., Burakoff, S. J., Dorf, M., et al. (1977) · The Journal of Experimental Medicine · doi:10.1084/jem.145.5.1387 · Cited by 55 · see citing works
Inflammation Enhances IL-2 Driven Differentiation of Cytolytic CD4 T Cells
Workman, A. M., Jacobs, A., Vogel, A. J., Condon, S. A., & Brown, D. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089010 · Cited by 49 · see citing works
CD4 T Cells Mediate Killing during Persistent Gammaherpesvirus 68 Infection
Stuller, K. A., & Flaño, E. (2009) · Journal of Virology · doi:10.1128/jvi.02240-08 · Cited by 48 · see citing works
Induction of I Region-Restricted Hapten-Specific Cytotoxic T Lymphocytes
Wagner, H., Starzinski‐Powitz, A., Jung, H., et al. (1977) · The Journal of Immunology · doi:10.4049/jimmunol.119.4.1365 · Cited by 48 · see citing works
Features of target cell lysis by class I and class II MHC-restricted cytolytic T lymphocytes.
Maimone, M. M., Morrison, L. A., Braciale, V. L., et al. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.137.11.3639 · Cited by 43 · see citing works
Gao, J., De, B. P., & Banerjee, A. K. (1999) · Journal of Virology · doi:10.1128/jvi.73.2.1411-1418.1999 · Cited by 43 · see citing works
Graham, C. M., Christensen, J. R., & Thomas, D. B. (2007) · Immunology · doi:10.1111/j.1365-2567.2007.02563.x · Cited by 27 · see citing works
Klucar, P., Barnes, P. F., Kong, Y., Samten, B., Tvinnereim, A., Spallek, R., Nepom, G. T., Singh, M., & Shams, H. (2008) · Human Immunology · doi:10.1016/j.humimm.2008.05.008 · Cited by 19 · see citing works
Valle‐Rios, R., Patiño‐López, G., Contreras, O. M., et al. (2009) · Molecular Immunology · doi:10.1016/j.molimm.2009.07.016 · Cited by 15 · see citing works
CRTAM is negatively regulated by ZEB1 in T cells
Rojas-Marquez, C., Valle‐Rios, R., López‐Bayghen, E., et al. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2015.03.253 · Cited by 9 · see citing works
Flagged first, then by citations
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Sorted by citations
Roles of IFN-γ in tumor progression and regression: A review
Jorgovanovic, D., Song, M., Wang, L., & Zhang, Y. (2020) · Biomarker Research · doi:10.1186/s40364-020-00228-x · Cited by 1,234 · see citing works
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531 · see citing works
Cytotoxic CD4+ T cells in cancer: Expanding the immune effector toolbox
Oh, D. Y., & Fong, L. (2021) · Immunity · doi:10.1016/j.immuni.2021.11.015 · Cited by 467 · see citing works
COVID-19 vaccines: The status and perspectives in delivery points of view
Chung, J. Y., Thone, M. N., & Kwon, Y. J. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.12.011 · Cited by 375 · see citing works
Śledzińska, A., Vila de Mucha, M., Bergerhoff, K., Hotblack, A., Demane, D. F., Ghorani, E., Akarca, A. U., Marzolini, M. A. V., Solomon, I., Vargas, F. A., et al. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.007 · Cited by 228 · see citing works
Johnson, D. B., McDonnell, W. J., Gonzalez-Ericsson, P. I., Al-Rohil, R. N., Mobley, B. C., Salem, J.-E., Wang, D. Y., Sanchez, V., Wang, Y., Chastain, C. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0523-2 · Cited by 176 · see citing works
Varghese, S., Pramanik, S., Williams, L. J., Hodges, H. R., Hudgens, C. W., Fischer, G. M., Luo, C. K., Knighton, B., Tan, L., Lorenzi, P. L., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0430 · Cited by 171 · see citing works
“Anti-CTLA4 and anti-PD1 have earlier been shown to potently increase proliferation of CD4þ T cells (33).”
Cytokine and Chemokine Signals of T‐Cell Exclusion in Tumors
Zhang, Y., Guan, X.-Y., & Jiang, P. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.594609 · Cited by 133 · see citing works
Wang, Y., Chen, Z., Wang, T., Guo, H., Liu, Y., Dang, N., Hu, S., Wu, L., Zhang, C., Ye, K., et al. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-00615-2 · Cited by 82 · see citing works
Sittplangkoon, C., Alameh, M.-G., Weissman, D., Lin, P. J. C., Tam, Y. K., Prompetchara, E., & Palaga, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.983000 · Cited by 79 · see citing works
“CTL recognizes target cells via peptide-MHC II complex on APCs (53).”
BackgroundInfluentialGlaser, V., Flugel, C., Kath, J., Du, W., Drosdek, V., Franke, C., Stein, M., Pruß, A., Schmueck-Henneresse, M., Volk, H.-D., et al. (2023) · Genome biology · doi:10.1186/s13059-023-02928-7 · Cited by 65 · see citing works
Liu, J., Yu, Q., Wu, W., Huang, X., Broering, R., Werner, M., Roggendorf, M., Yang, D., & Lu, M. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1700540 · Cited by 50 · see citing works
Histone deacetylases 1 and 2 restrain CD4+ cytotoxic T lymphocyte differentiation
Preglej, T., Hamminger, P., Luu, M., Bulat, T., Andersen, L., Göschl, L., Stolz, V., Rica, R., Sandner, L., Waltenberger, D., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.133393 · Cited by 36 · see citing works
Alshebremi, M., Tomchuck, S. L., Myers, J. T., Kingsley, D. T., Eid, S., Abiff, M., Bonner, M., Saab, S. T., Choi, S. H., & Huang, A. Y.-C. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006608 · Cited by 14 · see citing works
- Authors
- Takeuchi, A., & Saito, T.
- Affiliations
- RIKEN Center for Integrative Medical Sciences (JP)
- Corresponding author
- Saito, Takashi
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2017-02-23
- Volume
- 8
- Pages
- 194-194
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC5321676
- OpenAlex
- W2589191322
- Cited by
- 431
- References
- 69
- Citations by year
- 2026: 22 · 2025: 38 · 2024: 56 · 2023: 61 · 2022: 66 · 2021: 67 · 2020: 43 · 2019: 33 · 2018: 38 · 2017: 7
- FWCI
- 3.46
- 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)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (23790551 and 24229004)
- 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
- cytotoxic CD4+ T cells, CD4+ T cell differentiation, granzyme B, perforin, MHC class II restriction, CRTAM, naive T cells, Th1 cells, Eomesodermin, T-bet, antiviral immunity, antitumor immunity, inflammation, T cell subsets
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