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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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Cites
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BackgroundLymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
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Masopust, D., Vezys, V., Marzo, A. L., & Lefrançois, L. (2001) · Science · doi:10.1126/science.1058867 · Cited by 1,952 · cited 5×
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BackgroundInfluentialCD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs
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BackgroundInfluential
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“Tissue-resident memory T cells (TRM cells) are characterized by the expression of the C-type lectin CD69+ and/or the integrin CD103+ [54,55].”
BackgroundThe Function of Memory CD8+ T Cells in Immunotherapy for Human Diseases
Choi, H., Kim, Y., & Jung, Y. W. (2023) · Immune Network · doi:10.4110/in.2023.23.e10 · Cited by 16
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BackgroundGondé, H., Demeules, M., Hardet, R., Scarpitta, A., Junge, M., Pinto-Espinoza, C., Varin, R., Koch-Nolte, F., Boyer, O., & Adriouch, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.704408 · Cited by 11
“conjugated mAb against CD69, a marker that is highly expressed by many tissue resident T cells but by only few if any vascular T cells (35, 36).”
BackgroundT cell responses to SARS-CoV-2 in humans and animals
Mattoo, S.-U.-S., & Myoung, J. (2022) · The Journal of Microbiology · doi:10.1007/s12275-022-1624-z · Cited by 13
“Lung residential memory T cells (TRM) were shown to be critical mediators for protection against secondary viral infections (Schenkel and Masopust, 2014).”
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“T RM cells are enriched on mucosal surfaces with a heavy pathogen burden, such as on the skin, lungs, and gastrointestinal tract (29, 30).”
Malignant and Benign T Cells Constituting Cutaneous T-Cell Lymphoma
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Tissue residency of memory CD8+ T cells matters in shaping immunogenicity of ovarian cancer
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Niemietz, P. M., Peiseler, M., Kohlhepp, M. S., Horn, P., Matchett, K. P., Wang, Y., Haas, L., Zhang, T., Bruneau, A., Guillot, A., et al. (2024) · Hepatology · doi:10.1097/hep.0000000000000757 · Cited by 13
Alarm Functions of PD-1+ Brain-Resident Memory T Cells
Musial, S. C., Kleist, S. A., Degefu, H. N., Ford, M. A., Chen, T., Isaacs, J. F., Boussiotis, V. A., Skorput, A. G. J., & Rosato, P. C. (2024) · The Journal of Immunology · doi:10.4049/jimmunol.2400295 · Cited by 12
Wang, M., Qiao, Y., Wei, S.-J., Su, Z., & Lu, H. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1388814 · Cited by 14
Triggering mouth-resident antiviral CD8+ T cells potentiates experimental periodontitis
Saavedra, F. M., Brotto, D. B., Joag, V., Matson, C. A., Nesmiyanov, P. P., Herzberg, M. C., Vezys, V., Masopust, D., & Stolley, J. M. (2025) · Mucosal Immunology · doi:10.1016/j.mucimm.2025.02.003 · Cited by 12
“Viral infection in SPF mice, however, results in the differentiation, redistribution, and permanent establishment of CD8 + T RM in many mucosal tissues where they durably maintain regional antiviral vigilance 18–20 .”
Self-citationDosset, M., Joseph, E. L. M., Vargas, T. R., & Apétoh, L. (2020) · Cells · doi:10.3390/cells9071727 · Cited by 12
“Recently, a novel population of memory T cells usually characterized by core phenotypic markers CD45RO+CD69+CD103+/- [82,83] and the constitutive expression of checkpoint receptors (ICPs) [84–87] was defined as tissue-resident memory T cells (TRM) (Figure 2).”
BackgroundYu, S., Lao, S., Yang, B., & Wu, C. Y. (2021) · Journal of Immunology Research · doi:10.1155/2021/6643808 · Cited by 12
Context- and Tissue-Specific Regulation of Immunity and Tolerance by Regulatory T Cells
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Role of Dietary Metabolites in Regulating the Host Immune Response in Gastrointestinal Disease
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Induction of Effective Immunity against Trypanosoma cruzi
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“It should be noted that tissue-resident memory T cells act fast locally; however, they normally cannot survive in recipient mice because they lose association with the support environments once they are isolated (45).”
BackgroundVitamin D and immunomodulation in the skin: a useful affirmative nexus
Samanta, S. (2021) · Exploration of Immunology · doi:10.37349/ei.2021.00009 · Cited by 15
“59], express cutaneous lymphocyte-associated antigen and make the first-line defense against pathogenic invaders [60].”
BackgroundTissue resident memory T cells inhabit the deep human conjunctiva
Arnous, R., Arshad, S., Sandgren, K. J., Cunningham, A. L., Carnt, N. A., & White, A. (2022) · Scientific Reports · doi:10.1038/s41598-022-09886-3 · Cited by 14
Ichiki, Y., Fukuyama, T., Ueno, M., Kanasaki, Y., Goto, H., Takahashi, M., Mikami, S., Kobayashi, N., Nakanishi, K., Hayashi, S., et al. (2022) · Translational Lung Cancer Research · doi:10.21037/tlcr-22-421 · Cited by 11
Morrot, A. (2016) · Annals of Translational Medicine · doi:10.21037/atm.2016.05.38 · Cited by 12
Exhausted PD-1+ TOX+ CD8+ T Cells Arise Only in Long-Term Experimental Trypanosoma cruzi Infection
Gálvez, R. I., & Jacobs, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.866179 · Cited by 10
Viscidi, R. P., Rowley, T., & Bossis, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24129851 · Cited by 11
“Tissue-resident memory T cells occupy tissues without recirculating and provide the first response to infectious agents, accelerating pathogen clearance [10,11,85,86].”
BackgroundYamakawa, M., & Rexach, J. E. (2024) · Biomedicines · doi:10.3390/biomedicines12020308 · Cited by 14
“…subclusters were then annotated into their subtypes and states using markers manually curated from the literature to represent distinct types of tissue-resident lymphocytes (Supplementary Table S1), such as NCAM1 for NK cells, CD8A/B for CD8 T cells, and PRF1 and GZMA for cytotoxic cells [31–35].”
BackgroundMethodManchester, A. C., Ammons, D. T., Lappin, M. R., & DOW, S. W. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1397590 · Cited by 11
“The cluster annotated as GZMA high T cells exhibited overexpression of effector molecules (GZMA, GZMB) and integrins (ITGB7, ITGAE) which is suggestive of an intestinal mucosal tissue resident T cell phenotype (52 – 54).”
BackgroundImmunity to fungi and vaccine considerations
Whitehead, A. J., Woodring, T. S., & Klein, B. S. (2024) · Cell Host & Microbe · doi:10.1016/j.chom.2024.09.011 · Cited by 11
Research progress of mosquito-borne virus mRNA vaccines
Sun, N., Su, Z., & Zheng, X. (2024) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2024.101398 · Cited by 11
JAK inhibition and axial spondyloarthritis: new steps on the path to understanding pathophysiology
Ciccia, F., McGonagle, D., Thomas, R., Marzo-Ortega, H., Martin, D. A., Yndestad, A., & Volkov, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1488357 · Cited by 11
“IFN a , IFN b , IL-7, and IL-15 are involved in CD8 + T RM cell formation (101).”
Immunological memory: ILC1s come into view
Chen, Y., Tian, Z., & Peng, H. C. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0311-4 · Cited by 11
IL-21 in Homeostasis of Resident Memory and Exhausted CD8 T Cells during Persistent Infection
Ren, H. M., & Lukacher, A. E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186966 · Cited by 13
“, neoplasia and persistent infection) [17,18].”
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Regulatory T cells in inflamed liver are dysfunctional in murine primary biliary cholangitis
Lin, C., Wang, Y., Liu, C.-Y., Chen, H., Liang, P., & Chuang, Y. (2023) · Clinical & Experimental Immunology · doi:10.1093/cei/uxad117 · Cited by 11
Vogel, A. J., & Brown, D. M. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00327 · Cited by 11
Self-reactivity as the necessary cost of maintaining a diverse memory T-cell repertoire
Singh, N. J. (2016) · Pathogens and Disease · doi:10.1093/femspd/ftw092 · Cited by 11
“While the factors regulating the pool of tissue resident cells (TRM) are not well understood (Schenkel and Masopust 2014), the long-lived cells in the lymph nodes, spleen and bone marrow are thought to be maintained with the help of trophic factors that support a slow homeostatic turnover of the cells (Schluns and Lef…”
BackgroundIL‐15‐deficient mice develop enhanced allergic responses to airway allergen exposure
Mathias, C. B., Schramm, C. M., Guernsey, L. A., Wu, C. A., Polukort, S., Rovatti, J., Ser‐Dolansky, J., Secor, E. R., Schneider, S. S., Thrall, R. S., et al. (2017) · Clinical & Experimental Allergy · doi:10.1111/cea.12886 · Cited by 11
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Nguyen, S., Sada-Japp, A., Petrovas, C., & Betts, M. R. (2020) · Molecular Immunology · doi:10.1016/j.molimm.2020.05.016 · Cited by 12
“distinct transcriptional and functional signatures, and play a crucial role as sentinels within their local milieu upon antigenic re-exposure, reinfection, or reactivation in the case of chronic/episodic pathogens; for thorough reviews of TRM biology see (Gebhardt et al., 2018; Masopust and Soerens, 2019; Schenkel and…”
To Remember or to Forget: The Role of Good and Bad Memories in Adoptive T Cell Therapy for Tumors
Mondino, A., & Manzo, T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01915 · Cited by 11
“These have been described among CD4 and CD8 T cell subsets as being able to remain positioned within non-lymphoid tissues after Ag clearance and lack recirculation capacities (16, 17, 24).”
BackgroundMalhotra, D., Burrack, K. S., Jenkins, M. K., & Frosch, A. E. P. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02125 · Cited by 11
“With increasing evidence of the importance of residency in CD4 T cell memory, we stained for CD49a, which, similar to CD69 (8), has been used to define tissue residence in macrophages, NK cells, CD4 T cells, and CD8 T cells (9–14).”
BackgroundMethodResultInfluentialNavigating the diverse immune landscapes of psoriatic arthritis
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Gallego-Cortés, A., Sánchez-Gaona, N., Mancebo-Pérez, C., Ruiz-Isant, O., Benítez-Martínez, A., Landolfi, S., Castellví, J., Pumarola, F., Ortiz, N., Llano, I., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65288-9 · Cited by 12
“T RM can also express the adhesion molecules integrin α E (CD103) and integrin α 1 (CD49a), the immune checkpoint receptor PD-1, and the IL7 receptor-alpha chain (CD127) 47,51,52 .”
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Rattan, A., White, C. L., Nelson, S. A., Eismann, M., Padilla-Quirarte, H. O., Glover, M. A., Dileepan, T., Marathe, B. M., Govorkova, E. A., Webby, R. J., et al. (2022) · Pathogens · doi:10.3390/pathogens11020251 · Cited by 9
“CD69 negative T cells have been found at memory [84,90], arguing that these cells do not reflect kinetic intermediates.”
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“Researchers found that the function of memory T cells can be further finely defined by explicating those newly found subsets, like T RM , T memory stem cells (T SCM ), and virtual memory T cells (T VM ) [10–12].”
Mellors, P. W., Lange, A. N., Remondo, B. C., Shestov, M., Planer, J. D., Peterson, A. R., Ying, Y., Zhou, S., Christie, J. D., Diamond, J. M., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.176596 · Cited by 10
Heterogeneity of HIV-1 latent reservoirs
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“Resident memory T cells (TRM) are widely distributed in tissues but only petrol in a limited area, expressing specific homing receptors and providing local surveillance and protection.([14]) It is recently reported that TRM cells are also targets of HIV-1 infection and sites of viral persistence, but their roles inHIV…”
BackgroundInitiation, Persistence and Exacerbation of Food Allergy
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“These cells, first identified in epithelial barrier tissues such as the skin, lung, and gut, are long lived; persist in specific tissues; and provide protection against an array of bacterial, viral, fugal, and parasitic pathogens (14).”
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“We show that nematode-cured mice harbor memory Th2 cells in lymphoid and non-lymphoid organs with distinct transcriptional profiles, expressing recirculation markers like CCR7 and CD62-L in the mesenteric lymph nodes (mLN), and costimulatory markers like Ox40, as well as tissue homing and activation markers like CCR2,…”
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SARS-CoV-2 mRNA vaccination–induced immunological memory in human nonlymphoid and lymphoid tissues
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“, 2017), central memory T (TCM), effector memory T (TEM), and tissue-resident memory (TRM) (Sallusto et al., 1999; Schenkel and Masopust, 2014).”
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“1+Foxp3- CD4 T cells in the lung parenchyma, we analyzed lungs from memory mice on day 68 without allergen rechallenge looking for common markers of tissue-residency (Beura and Masopust, 2014; Schenkel and Masopust, 2014).”
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CD8+ T cells pump the brakes on Alzheimer’s disease
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Divergent behavior of mucosal memory T cells
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Markov process models of the dynamics of HIV reservoirs
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IL-12 mRNA-LNP promotes dermal resident memory CD4+ T cell development
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Epigenetic control of tissue resident memory T cells
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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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