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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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“Tem cells also lack LN homing receptors (CD62L and CCR7), yet expressed distinct patterns of other homing receptors, and on that basis it was proposed that Tem cells recirculate between blood and nonlymphoid tissues (NLTs) or remain poised to mobilize to sites of inflammation (Butcher and Picker, 1996; Mackay et al.,…”
BackgroundLymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
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“Similarly, dendritic cells upregulate CCR7 after activation in tissues, which then acts in concert with S1PR1 to promote migration to downstream SLOs (Braun et al., 2011; Czeloth et al., 2005; Lamana et al., 2011; Ohl et al., 2004; Saeki et al., 1999).”
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BackgroundInfluential
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“For cell differentiation, T cells were stimulated with anti-CD3/CD28 beads (cell/bead ratio = 2/1; Thermo Fisher Scientific, Lenexa, USA) in the presence or absence of mitochondrial division inhibitor-1 (Mdivi-1) (50 µM) for 4 days, followed by analyses of lineage-determining transcription factors and surface marker C…”
InfluentialImmunological Control of Herpes Simplex Virus Type 1 Infection: A Non-Thermal Plasma-Based Approach
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“…residency, lung BRMs, unlike their circulating counter-parts, exhibit hallmark features of local retention, including the upregulation of CD69 and the concurrent downregulation of S1PR1 [3, 142 – 146], a receptor that promotes lymphocyte egress from tissues into the circulation [143, 147, 148].”
Krüppel-like factors 2 and 3 regulate T cell exhaustion by directing T cell residency and migration
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Multiple subsets of regulatory T-cells
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“There are three major subsets of memory T cells as de fi ned by recent studies, which are termed central memory T cells (Tcm), effector memory T cells (Tem), and tissue resident memory T cells (Trm) (11, 12).”
BackgroundModulation of CD4+ T Helper Cell Memory Responses in the Human Skin
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Editorial: Bone Marrow T Cells at the Center Stage in Immunological Memory
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“Although these variations have been associated with changes in scar formation, reactogenicity, and immune response pro fi les, their impact on overall vaccine ef fi cacy remains inconclusive (105, 107,108,109,110,111).”
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“These include two subsets of circulating populations – central memory T (T CM ) and effector memory T (T EM ) cells – and one subset that stably occupies peripheral tissues - tissue resident memory T (T RM ) cells (52 – 54).”
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“CD103 ( a E integrin), a receptor for E-Cadherin, is predominantly expressed on intestinal CD8 + TRM cells, where it promotes the residency of TRM cells (22).”
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“In contrast to TRM cells in liv r, a la ge fraction of TRM cells in the intraepithelial compartment of the small intestine expressed CD103 [34].”
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“CD4 + CD44 + memory T cells could generally be divided into three subtypes: tissue-resident memory T (TRM) cells and two types of circulating memory T cells: effector memory T (TEM) and central memory T (TCM) cells [12, 13].”
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“…tissues where they are described to (1) persist with a peri- or intra-epithelial localization, (2) participate in the control of local cognate infections, and (3) promote the recruitment of new immune cells to the area in an interferon-g (IFN-g)-dependent manner (Schenkel and Masopust, 2014).”
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Lung-resident memory CD4+ T cells are dependent on Batf3
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“Although these hepatic TRM cells might have some potential to reenter the circulation as recently demonstrated for thymic CD69+CD103− memory CD8+ T cells (44), the observation of an increased accumulation of this cell subset in the liver emphasized the general appropriateness of this marker (21, 43, 45).”
BackgroundLakshmanappa, Y. S., Roh, J. W., Rane, N. N., Dinasarapu, A. R., Tran, D. D., Velu, V., Sheth, A. N., Ofotokun, I., Amara, R. R., Kelley, C. F., et al. (2021) · FEBS Letters · doi:10.1002/1873-3468.14163 · Cited by 5
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Cognate antigen-independent differentiation of resident memory T cells in chronic kidney disease
Moore, K. H., Erman, E. N., Traylor, A., Esman, S. K., Jiang, Y., LaFontaine, J. R., Zmijewska, A. A., Lu, Y., Soliman, R. H., Agarwal, A., et al. (2024) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00373.2023 · Cited by 4
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Crosstalk between CD8+ T cells and mesenchymal stromal cells in intestine homeostasis and immunity
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Isolation and Characterization of Human Tissue Resident Memory T cells
Jensen, I. J., Wells, S. B., Gras, J., & Färber, D. L. (2025) · Current Protocols · doi:10.1002/cpz1.70120 · Cited by 4
“…robust local immune responses within tissue by utilizing various mechanisms, such as direct effector function, the recruitment of additional immune cells, and enhancement of effector cell priming in tissue-associated lymph nodes (Paik & Farber, 2020; Schenkel & Masopust, 2014; Szabo et al., 2019).”
Antigen-specific memory and naïve CD4+ T cells following secondary Chlamydia trachomatis infection
Helble, J. D., Mann, A. O., & Starnbach, M. N. (2020) · PLoS ONE · doi:10.1371/journal.pone.0240670 · Cited by 5
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“Depending on their expression of surface markers, gene transcription, location, and role in immunity, they can further be classified mainly into central memory cells (TCM), effector memory cells (TEM), and tissue resident memory cells (TRM) [9].”
BackgroundChihara, N., Tsuji, A., & Matsumoto, R. (2023) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12747 · Cited by 4
Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice
Qin, L., Li, Q., Wang, L., & Huang, Y. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1253188 · Cited by 4
“These cells mediate ex vivo cytotoxicity or clear pathogens through non-cytolytic approaches (19, 20).”
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Molecular exaptation by the integrin αI domain
Hollis, J. A., Chan, M. C., Malik, H. S., & Campbell, M. G. (2025) · Science Advances · doi:10.1126/sciadv.adx9567 · Cited by 4
Pathogenic drivers of lupus myocarditis and potential therapeutic targets
Liu, Y., Murphy, K. M., Hung, Y. F., & Won, T. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01580-4 · Cited by 3
“Tissue-resident memory T (T RM ) cells are a subset of memory T cells that reside in peripheral tissues without recirculation and provide immediate immune responses upon re-exposure to antigens 81 .”
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The Central Role of Macrophages in Long COVID Pathophysiology
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“Thus, some researchers have proposed the concept of T-cell exhaustion as a dynamic progression from a long-lived “preexhausted stem-like progenitor” state to a “terminally exhausted” state [6, 10].”
Molecular requirements of pathogenic Th2 cell differentiation in allergic airway disease
Khan, M., Fuhrmann, V., Cavanagh, L. L., & Boucheron, N. (2026) · Immunology Letters · doi:10.1016/j.imlet.2026.107143 · Cited by 6
Tissue-specific clonal selection and differentiation of CD4⁺ T cells during infection
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Mucosal Vaccine Development: From Adjuvant Design to Next-Generation Delivery Strategies
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“Tissue-resident memory T (T RM ) cells are non-circulating memory T cells that permanently reside in peripheral tissues, including mucosal surfaces [34,35].”
The Role of Tissue Resident Memory Cells in Immunodermatological Disorders
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Mucosal immunity and vaccine development
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“48, 49 When restimulated by antigens, T RM cells can be rapidly activated and exhibit effector activities, hence offering a frontline protection against pathogens at entry sites.”
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Tissue-Resident Memory T Cells in Tumor Immunity and Immunotherapy of Digestive System Tumors
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“TRM cell subsets include CD4 + T cells, NKT cells, and mucosal-associated invariant T (MAIT) cells (Mueller & Mackay, 2016; Schenkel & Masopust, 2014).”
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Some vexations that challenge viral immunology
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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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