Cited by 1,059T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisImmunotherapy and Immune Responses

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Tissue-Resident Memory T Cells

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Schenkel, Jason M., Masopust, David·2014·Immunity

DOI 10.1016/j.immuni.2014.12.007PMC PMC4276131

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Abstract

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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BackgroundResultInfluentialSelf-citation
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BackgroundInfluential
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BackgroundInfluential

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Lee‐Sayer, S. S. M., Maeshima, N., Dougan, M. N., Dahiya, A., Arif, A. A., Dosanjh, M., Maxwell, C. A., & Johnson, P. (2018) · European Journal of Immunology · doi:10.1002/eji.201747263 · Cited by 25
Citrobacter rodentium Induces Tissue-Resident Memory CD4 + T Cells
Bishu, S., Hou, G., Zaatari, M. E., Bishu, S. R., Popke, D. S., Zhang, M., Grasberger, H., Zou, W., Stidham, R. W., Higgins, P., et al. (2019) · Infection and Immunity · doi:10.1128/iai.00295-19 · Cited by 24
“maintain expression of the activation markers CD44 and CD69 (20, 21).”
BackgroundInfluential
Gastric Subserous Vaccination With Helicobacter pylori Vaccine: An Attempt to Establish Tissue-Resident CD4+ Memory T Cells and Induce Prolonged Protection
Liu, W., Zeng, Z., Luo, S., Hu, C., Xu, N., Huang, A., Zheng, L., Sundberg, E. J., Xi, T., & Xing, Y. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01115 · Cited by 25
“3% lymphocytes loss in stomach using flow cytometry for counting (2, 39).”
Method
Longevity of vaccine protection: Immunological mechanism, assessment methods, and improving strategy
Chen, Z., Gao, X., & Yu, D. (2022) · Open Research (University of Surrey) · doi:10.1002/viw.20200103 · Cited by 30
Memory B‐cell diversity: From early generation to tissue residency and reactivation
Reusch, L., & Angeletti, D. (2023) · European Journal of Immunology · doi:10.1002/eji.202250085 · Cited by 27
Reverse transendothelial cell migration in inflammation: to help or to hinder?
Burn, T. N., & Alvarez, J. I. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2444-2 · Cited by 28
Interferon-Gamma Modulation of the Local T Cell Response to Alphavirus Encephalomyelitis
Baxter, V. K., & Griffin, D. E. (2020) · Viruses · doi:10.3390/v12010113 · Cited by 25
“Tissue-resident memory (TRM) cells are a subset of memory T cells that do not circulate, but instead permanently remain at sites of infection [37].”
Background
CD4+ Memory T-Cell Formation during Type 1 Immune ResponsesPreprint
Krueger, P. D., Osum, K. C., & Jenkins, M. K. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a038141 · Cited by 25
Tissue-resident memory T cells in protective immunity to influenza virus
Lee, S., Yeung, K., & Watts, T. H. (2024) · Current Opinion in Virology · doi:10.1016/j.coviro.2024.101397 · Cited by 24
Phenotypical and potential functional characteristics of different immune cells expressing CD28H/B7-H5 and their relationship with cancer prognosis
Zhong, C., Lang, Q., Yu, J., Wu, S., Xu, F., & Tian, Y. (2020) · Clinical & Experimental Immunology · doi:10.1111/cei.13413 · Cited by 23
Runx proteins and transcriptional mechanisms that govern memory CD8 T cell development
Pipkin, M. E. (2021) · Immunological Reviews · doi:10.1111/imr.12954 · Cited by 24
Long non-coding RNA: An underlying bridge linking neuroinflammation and central nervous system diseases
Chen, Z., Wu, H., & Zhang, M. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105101 · Cited by 24
Differential Fuel Requirements of Human NK Cells and Human CD8 T Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T Cells
Presnell, S. R., Spear, H. K., Durham, J., Riddle, T., Applegate, A., & Lutz, C. T. (2020) · ImmunoHorizons · doi:10.4049/immunohorizons.2000020 · Cited by 24
TIGIT Deficiency Protects Mice From DSS-Induced Colitis by Regulating IL-17A–Producing CD4+ Tissue-Resident Memory T Cells
Chen, B., Ye, B., Li, M., Wang, S., Li, J., Lai, Y., Yang, N., Ke, Z., & Zhang, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.931761 · Cited by 25
“TRM cells are characterized by the expression of C-type lectin CD69, which counteracts sphingosine 1 phosphate receptor 1–mediated tissue egress and promotes tissue residency (13).”
Background
The role of antiviral CD8+ T cells in cognitive impairment
Reagin, K. L., & Funk, K. E. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2022.102603 · Cited by 24
Maintenance and recall of memory T cell populations against tuberculosis: Implications for vaccine design
Liu, X., Li, H., Li, S., Yuan, J., & Pang, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1100741 · Cited by 25
“TRMs can be distinguished from circulating Tm cells by their high-level cell surface expression of CD69 and CD103 molecules (27), while their functions and transcriptional expression profiles resemble corresponding features of TCM and TEM cells (28).”
Background
Role of T cell—glial cell interactions in creating and amplifying central nervous system inflammation and multiple sclerosis disease symptoms
Huseby, E. S., Kamimura, D., Arima, Y., Parello, C. S. L., Sasaki, K., & Murakami, M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00295 · Cited by 25
Differentiating Immune Cell Targets in Gut-Associated Lymphoid Tissue for HIV Cure
Khan, S., Telwatte, S., Trapečar, M., Yukl, S. A., & Sanjabi, S. (2017) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2017.0153 · Cited by 27
Lymph node γδ and αβ CD8+ T cells share migratory properties
Ugur, M., Kaminski, A., & Pabst, O. (2018) · Scientific Reports · doi:10.1038/s41598-018-27339-8 · Cited by 25
Spatial and temporal coordination of antiviral responses by group 1 ILC s
Adams, N. M., & Sun, J. C.-Y. (2018) · Immunological Reviews · doi:10.1111/imr.12710 · Cited by 23
Divergent Effects of a Transient Corticosteroid Therapy on Virus-Specific Quiescent and Effector CD8+ T Cells
Kumar, D., & Sehrawat, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01521 · Cited by 24
“For many infections this population serves as the initial responder and eventually help resolve the infection quickly (13, 24, 42).”
Background
Engineering Vaccines for Tissue‐Resident Memory T Cells
Knight, F. C., & Wilson, J. T. (2021) · Advanced Therapeutics · doi:10.1002/adtp.202000230 · Cited by 24
Building conventions for unconventional lymphocytes
Pasman, L., & Kasper, D. L. (2017) · Immunological Reviews · doi:10.1111/imr.12576 · Cited by 23
Single-Cell Analysis Reveals Characterization of Infiltrating T Cells in Moderately Differentiated Colorectal Cancer
Yang, X., Quan, Q., Pan, Y., Zhou, Q., Wu, Y., Zhuang, J., Xu, J., Pan, M., & Han, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.620196 · Cited by 24
“TRMT cells are a recently found lymphocyte lineage specialized by some memory T cells for life and function within tissues (not present within peripheral blood) (31).”
Background
Immunobiology of the biliary tract system
Björkström, N. K. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.08.018 · Cited by 26
“The liver is enriched with innate immune cells including specialised macrophages, NK cells, and unconventional T cells, many of which appear to be tissue resident. exhibit functional roles in retaining immune cells in tissues (reviewed in 25,26 ).”
Background
E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function
Wei, Y., Han, S., Wen, J., Liao, J., Liang, J., Yu, J., Chen, X., Xiang, S., Huang, Z., & Zhang, B. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00909-3 · Cited by 25
“Tissue-resident memory T cells (Trm) cells are a subset of CD8+ T cells which positions within nonlymphoid tissues without entering the peripheral blood [98].”
Background
Aging of Antiviral CD8+ Memory T Cells Fosters Increased Survival, Metabolic Adaptations, and Lymphoid Tissue Homing
Davenport, B., Eberlein, J., van der Heide, V., Jhun, K., Nguyen, T. T., Victorino, F., Trotta, A. P., Chipuk, J. E., Yi, Z., Zhang, W., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1801277 · Cited by 23
“Finally, in considering the role of CD8 TRM as highly effective first responders to infections re-encountered at body surfaces (70) and the established role of LN-residing CD8 TM as direct precursors for II ̊ CD8 TE expansions, it is worth noting that LN CD8 + TM themselves also act as gate-keepers and immediate effec…”
Background
Reactive glia promote development of CD103+CD69+ CD8+ T‐cells through programmed cell death‐ligand 1 (PD‐L1)
Prasad, S., Hu, S., Sheng, W. S., Chauhan, P., & Lokensgard, J. R. (2018) · Immunity Inflammation and Disease · doi:10.1002/iid3.221 · Cited by 24
Differential predictive value of resident memory CD8 + T cell subpopulations in patients with non-small-cell lung cancer treated by immunotherapy
Paolini, L., Tran, T., Corgnac, S., Villemin, J.-P., Wislez, M., Arrondeau, J., Johannes, L., Ulmer, J., Vieillard, L.-V., Pineau, J., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009440 · Cited by 29
Deciphering the deterministic role of TCR signaling in T cell fate determination
Qin, Z., & Xu, T. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1562248 · Cited by 30
“In addition to its role in memory formation and exhaustion, TCR signaling strength has also been implicated in tissue-resident memory T cell (TRM) differentiation (181).”
From the draining lymph node to the liver: the induction and effector mechanisms of malaria-specific CD8+ T cells
Radtke, A. J., Tse, S., & Zavala, F. P. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-015-0479-3 · Cited by 22
“Importantly, liver-resident memory CD8 T cells were homogenously CD69 and expressed lower levels of the transcription factors Eomes and KLF2, consistent with the tissueresident (Trm) phenotype recently reported [61].”
Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance
Dobson, H. E., Dias, L. D. S., Kohn, E. M., Fites, J. S., Wiesner, D. L., Dileepan, T., Kujoth, G. C., Abraham, A., Ostroff, G. R., Klein, B. S., et al. (2020) · Mucosal Immunology · doi:10.1038/s41385-019-0244-3 · Cited by 22
T cell responses toChlamydia
Helble, J. D., & Starnbach, M. N. (2021) · Pathogens and Disease · doi:10.1093/femspd/ftab014 · Cited by 23
Role of tissue-resident memory T cells in the pathophysiology of allergic contact dermatitis
Lefevre, M.-A., Vocanson, M., & Nosbaum, A. (2021) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000763 · Cited by 23
HIV-1 Genomes Are Enriched in Memory CD4 + T-Cells with Short Half-Lives
Morcilla, V., Bacchus, C., Fisher, K., Horsburgh, B. A., Hiener, B. M., Wang, X. Q., Schlub, T. E., Fitch, M. D., Hoh, R., Hecht, F. M., et al. (2021) · mBio · doi:10.1128/mbio.02447-21 · Cited by 23
“Less-characterized resident memory (TRM) T-cells are transcriptionally, phenotypically, and functionally distinct from recirculating memory cells and provide a first response against infections in tissue, where they accelerate pathogen clearance (48).”
Background
Phenotypic, functional, and metabolic heterogeneity of immune cells infiltrating non–small cell lung cancer
Aramini, B., Masciale, V., Samarelli, A. V., Dubini, A., Gaudio, M., Stella, F., Morandi, U., Dominici, M., Biasi, S. D., Gibellini, L., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.959114 · Cited by 23
“Moreover, TRM cells, found in the epithelial barriers, could also express aeb7 integrin for maintenance (the chain ae is also called CD103) [reviewed in (14)].”
Background
Engineered IL-15/IL-15R α -expressing cellular vesicles promote T cell anti-tumor immunity
Fang, W., Li, L., Lin, Z., Zhang, Y., Jing, Z., Li, Y., Zhang, Z., Hou, L., Liang, X., Zhang, X., et al. (2022) · Extracellular Vesicle · doi:10.1016/j.vesic.2022.100021 · Cited by 22
Tissue-resident memory T cells in renal autoimmune diseases
Ginsberg, P., Panzer, U., & Asada, N. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1111521 · Cited by 22
“Tissue-resident memory T cells (TRM cells) are a recently identified lymphocyte subset that resides in peripheral organs for long time periods (1, 2).”
Background
Mitochondrial Control of Proteasomal Psmb5 Drives the Differentiation of Tissue‐Resident Memory T Cells in Patients with Rheumatoid Arthritis
Wu, T., Su, D., Zhang, L., Liu, T., Wang, Q., Yan, C., Liu, M., Ji, H., Lei, J., Zheng, M., et al. (2024) · Arthritis & Rheumatology · doi:10.1002/art.42954 · Cited by 21
IL-12 drives the expression of the inhibitory receptor NKG2A on human tumor-reactive CD8 T cells
Fesneau, O., Samson, K. A., Rosales, W. K., Jones, B., Moudgil, T. L., Fox, B. A., Rajamanickam, V., & Duhen, T. M. (2024) · Nature Communications · doi:10.1038/s41467-024-54420-w · Cited by 25
“Cells in the T2 subset displayed intermediate levels of PD-1 and expressed heterogenous levels of CD39, CD28, and CD127, a phenotype consistent with tissue resident memory T cells 28 – 30 .”
A pro-inflammatory CD8+ T-cell subset patrols the cervicovaginal tract
Pattacini, L., Davis, A. S. W., Czartoski, J., Mair, F., Presnell, S., Hughes, S. M., Hyrien, O., Lentz, G. M., Kirby, A. C., Fialkow, M. F., et al. (2019) · Mucosal Immunology · doi:10.1038/s41385-019-0186-9 · Cited by 20
Memory T Cells in Transplantation: Old Challenges Define New Directions
Nicosia, M., Fairchild, R. L., & Valujskikh, A. (2020) · Transplantation · doi:10.1097/tp.0000000000003169 · Cited by 23

Authors: Schenkel, J. M., & Masopust, D.
Affiliations: University of Minnesota (US)
Corresponding author: Masopust, David
ORCID: Schenkel, Jason M.
Masopust, David
Venue: Immunity
Publisher: Elsevier BV
Published: 2014-12
Volume: 41
Issue: 6
Pages: 886-897
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2014.12.007
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 382 d)
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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Tissue-Resident Memory T Cells

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