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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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BackgroundInfluential
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“This review will focus on the tissue adaptation of tissue-resident natural γδ T cells and adaptive γδ TRM cells in barrier tissues while highlighting their development, maintenance and role in health and disease. γδ T CELLS OF HUMANS AND MICE Murine γδ T cells are often segregated into different subsets based on their…”
BackgroundInfluentialT‐bet+ memory B cells: Generation, function, and fate
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“…αE-integrin, which pairs with β7-integrin to bind E-cadherin, is important for retention of some CD8+ and CD4+ Trm cells (Iijima and Iwasaki, 2015; Schenkel and Masopust, 2014), but TGF-β plays additional roles in promoting Trm cells, including negative regulation of T-bet and Eomes (Mackay et…”
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“These findings are consistent with the growing acceptance that the location of T cells can be important for their phenotype, as seen in memory cell subtypes such as tissue-resident memory T cells, which are important for the recall response to antigen 17,67,68 .”
ResultTranscriptional programming of tissue-resident memory CD8+ T cells
Milner, J. J., & Goldrath, A. W. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.03.017 · Cited by 123
Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease
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“Tissueresident memory T (Trm) cells persist in previously inflamed nonlymphoid tissue (NLT), providing enhanced local immune memory (Carbone, 2015; Schenkel and Masopust, 2014).”
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“In addition to their varying anatomical distributions, these memory cell subsets also display several unique phenotypical and functional properties (Low and Kaech, 2018; Schenkel and Masopust, 2014).”
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“This important subset is transcriptionally, phenotypically, and functionally distinct from circulating T cells (21, 24) but remains poorly characterized in humans.”
A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer
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Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine
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Delineation of a molecularly distinct terminally differentiated memory CD8 T cell population
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Surface phenotypes of naive and memory B cells in mouse and human tissues
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Tissue instruction for migration and retention of TRM cells
Iijima, N., & Iwasaki, A. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.07.002 · Cited by 121
Resident memory CD8+ T cells within cancer islands mediate survival in breast cancer patients
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“TRMs are a subset of T cells, either CD8 or CD4, that are retained and long-lived in peripheral tissues (36-38).”
BackgroundUpdate on Chlamydia trachomatis Vaccinology
de la Maza, L. M., Zhong, G., & Brunham, R. C. (2017) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00543-16 · Cited by 117
Gut immune cell trafficking: inter-organ communication and immune-mediated inflammation
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Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8+ T cells
Muschaweckh, A., Buchholz, V. R., Fellenzer, A., Hessel, C., Koenig, P.-A., Tao, S., Tao, R., Heikenwälder, M. F., Busch, D. H., Korn, T., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160888 · Cited by 113
Vitiligo: Mechanistic insights lead to novel treatments
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Pathogen-induced tissue-resident memory T H 17 (T RM 17) cells amplify autoimmune kidney disease
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“In contrast, the role of CD4+ TRM cells in peripheral tissues is less well characterized (24).”
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ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells
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TCR Signaling in T Cell Memory
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Stem, Effector, and Hybrid States of Memory CD8+ T Cells
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Blimp-1 Rather Than Hobit Drives the Formation of Tissue-Resident Memory CD8+ T Cells in the Lungs
Behr, F. M., Kragten, N. A. M., Wesselink, T. H., Nota, B., van Lier, R. A. W., Amsen, D., Stark, R., Hombrink, P., & van Gisbergen, K. P. J. M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00400 · Cited by 103
“Given their potency in limiting pathogen spread, insights into the mechanisms regulating the development and maintenance of CD8 TRM cells may contribute to improved strategies to induce protective immunity via vaccination (10, 11).”
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Dilated cardiomyopathy and chronic cardiac inflammation: Pathogenesis, diagnosis and therapy
Harding, D., Chong, M. H. A., Lahoti, N., Bigogno, C. M., Prema, R., MOHIDDIN, S. A., & Marelli‐Berg, F. M. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13556 · Cited by 109
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“They also proliferate rapidly and kill infected cells, protecting directly against local challenge.(3,4,5,8) It may therefore be important to elicit TRM cells as part of an effective vaccination strategy.”
BackgroundMemory T-Cell Heterogeneity and TerminologyPreprint
Muroyama, Y., & Wherry, E. J. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a037929 · Cited by 104
Human lung tissue resident memory T cells in health and disease
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“…that recirculate between tissues and the intravascular space via the lymphatic system ( 19 ), whereas anatomically localized immunity is primarily a function of tissue-resident memory T (T RM ) cells ( 20 ), which remain in situ and act as frontline defenders against patho-gen invasion ( 21 ).”
Assessing the generation of tissue resident memory T cells by vaccines
Rotrosen, E. T., & Kupper, T. S. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00853-1 · Cited by 91
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Same yet different — how lymph node heterogeneity affects immune responses
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Resident-Memory T Cells in Tissue-Restricted Immune Responses: For Better or Worse?
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“In order to unequivocally identify TRM, besides phenotypical analysis, functional experiments assessing TRM tissue egress, persistence, and their disequilibrium with peripheral TCM and TEM cells are usually performed (6, 35).”
BackgroundMurine CMV Infection Induces the Continuous Production of Mucosal Resident T Cells
Smith, C. J., Caldeira-Dantas, S., Turula, H., & Snyder, C. M. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.076 · Cited by 86
Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues
Kadoki, M., Patil, A., Thaiss, C. C., Brooks, D., Pandey, S., Deep, D., Álvarez, D., von Andrian, U. H., Wagers, A. J., Nakai, K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.024 · Cited by 85
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“The appreciation that memory T cells are abundant in human peripheral tissues, however, is relatively 272 recent (reviewed in (11, 14-16)).”
BackgroundRakhra, K., Abraham, W. D., Wang, C., Moynihan, K. D., Li, N., Donahue, N. D., Baldeon, A. D., & Irvine, D. J. (2021) · Science Immunology · doi:10.1126/sciimmunol.abd8003 · Cited by 87
Resident memory T cells and cancer
Gavil, N. V., Cheng, K., & Masopust, D. (2024) · Immunity · doi:10.1016/j.immuni.2024.06.017 · Cited by 104
Self-citationHost conditioning with IL-1β improves the antitumor function of adoptively transferred T cells
Lee, P., Yamamoto, T. N., Gurusamy, D., Sukumar, M., Yu, Z., Hu‐Li, J., Kawabe, T., Gangaplara, A., Kishton, R. J., Henning, A. N., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20181218 · Cited by 88
“Trm cells reside in the extralymphoid tissues and do not return into circulation (Schenkel and Masopust, 2014).”
BackgroundUpdate on the etiopathogenesis of psoriasis (Review)
Branisteanu, D. E., Cojocaru, C., Diaconu, R., Porumb‐Andrese, E., Alexa, A. I., Nicolescu, A. C., Brihan, I., Bogdănici, C. M., Brănișteanu, G., Dimitriu, A., et al. (2022) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2022.11124 · Cited by 87
Bone Marrow T Cells and the Integrated Functions of Recirculating and Tissue-Resident Memory T Cells
Rosa, F. D., & Gebhardt, T. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00051 · Cited by 88
Understanding memory CD8 + T cells
Samji, T., & Khanna, K. M. (2017) · Immunology Letters · doi:10.1016/j.imlet.2017.02.012 · Cited by 91
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Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions
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Targets of therapy in progressive MS
Lassmann, H. (2017) · Multiple Sclerosis Journal · doi:10.1177/1352458517729455 · Cited by 83
Lung Tissue Resident Memory T-Cells in the Immune Response to Mycobacterium tuberculosis
Ogongo, P., Porterfield, J. Z., & Leslie, A. J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00992 · Cited by 84
Single-cell transcriptome analysis identifies skin-specific T-cell responses in systemic sclerosis
Gaydosik, A. M., Tabib, T., Domsic, R. T., Khanna, D., Lafyatis, R., & Fuschiotti, P. (2021) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2021-220209 · Cited by 85
Hu, Y., Hudson, W. H., Kissick, H. T., Medina, C. B., Baptista, A. P., Ma, C., Liao, W., Germain, R. N., Turley, S. J., Zhang, N., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211574 · Cited by 86
“In addition, TGF-β induces expression of αEβ7 integrin (CD103) and is essential for the generation and/or residence of tissue-resident memory T (TRM) cells in many peripheral tissues (Schenkel and Masopust, 2014).”
BackgroundCutting Edge: Resident Memory CD8 T Cells Express High-Affinity TCRs
Frost, E. L., Kersh, A. E., Evavold, B. D., & Lukacher, A. E. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1501521 · Cited by 80
Carpenter, D. J., Granot, T., Matsuoka, N., Senda, T., Kumar, B. V., Thome, J. J. C., Gordon, C. L., Miron, M., Weiner, J. I., Connors, T. J., et al. (2017) · American Journal of Transplantation · doi:10.1111/ajt.14434 · Cited by 77
CD4+ Memory T Cells at Home in the Tissue: Mechanisms for Health and Disease
Schreiner, D., & King, C. G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02394 · Cited by 84
“More recently, an additional population of memory T cells localized within barrier tissues has been identified (8, 9).”
BackgroundBialkowski, L., van Weijnen, A., der Jeught, K. V., Renmans, D., Daszkiewicz, L., Heirman, C., Stangé, G. M., Breckpot, K., Aerts, J. L., & Thielemans, K. (2016) · Scientific Reports · doi:10.1038/srep22509 · Cited by 79
Prognostic and therapeutic TILs of cervical cancer—Current advances and future perspectives
Tang, Y. C., Zhang, A. X. J., Chen, G., Wu, Y., & Gu, W. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2021.07.006 · Cited by 81
Human T Cell Memory: A Dynamic View
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Chapin, C. A., Burn, T. N., Meijome, T. E., Loomes, K. M., Melín‐Aldana, H., Kreiger, P. A., Whitington, P. F., Behrens, E. M., & Alonso, E. M. (2018) · Hepatology · doi:10.1002/hep.29901 · Cited by 80
“Trm cells are a recently identified bona fide population of CD8 Tcells characterized to be a memory population that does not reside in secondary lymphoid tissue or in the circulation but rather resides in solid tissues.((20)) These cells are thought to be important in acting as first responders to infections attemptin…”
BackgroundGilchuk, P., Hill, T. M., Guy, C. S., McMaster, S. R., Boyd, K. L., Rabacal, W., Wang, L., Shyr, Y., Kohlmeier, J. E., Sebzda, E., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.07.037 · Cited by 77
“Hence, insights into the generation and function of TRM cells are essential for devising ways to induce protective immunity by vaccination (Clark, 2015; Schenkel and Masopust, 2014).”
BackgroundKimura, M. Y., Hayashizaki, K., Tokoyoda, K., Takamura, S., Motohashi, S., & Nakayama, T. (2017) · Immunological Reviews · doi:10.1111/imr.12559 · Cited by 82
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γδ T cell dichotomy with opposing cytotoxic and wound healing functions in human solid tumors
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“Since that time, it is clear that there is an additional population of tissue-resident memory lymphocytes that either do not recirculate, or re-circulate very slowly, and provide rapid responses to re-infection [83,84].”
BackgroundDeficient Resident Memory T Cell and CD8 T Cell Response to Commensals in Inflammatory Bowel Disease
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Boosting vaccine efficacy the natural (killer) way
Rydyznski, C. E., & Waggoner, S. N. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.07.004 · Cited by 72
“Given the current interest in tissue-resident memory T cells [105], it will be important to evaluate whether priming of these front-line sentinels is also modulated by NK cells.”
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Tissue-specific differentiation of CD8+ resident memory T cells
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Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection
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“lymphoid tissues in humans and mice (Schenkel and Masopust, 2014).”
Bishu, S., Zaatari, M. E., Hayashi, A., Hou, G., Bowers, N., Kinnucan, J. A. R., Manoogian, B., Muza–Moons, M. M., Zhang, M., Grasberger, H., et al. (2019) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjz010 · Cited by 76
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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