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Distribution and Compartmentalization of Human Circulating and Tissue-Resident Memory T Cell Subsets
Open accessAbstract
Knowledge of human T cells derives chiefly from studies of peripheral blood, whereas their distribution and function in tissues remains largely unknown. Here, we present a unique analysis of human T cells in lymphoid and mucosal tissues obtained from individual organ donors, revealing tissue-intrinsic compartmentalization of naive, effector, and memory subsets conserved between diverse individuals. Effector memory CD4(+) T cells producing IL-2 predominated in mucosal tissues and accumulated as central memory subsets in lymphoid tissue, whereas CD8(+) T cells were maintained as naive subsets in lymphoid tissues and IFN-γ-producing effector memory CD8(+) T cells in mucosal sites. The T cell activation marker CD69 was constitutively expressed by memory T cells in all tissues, distinguishing them from circulating subsets, with mucosal memory T cells exhibiting additional distinct phenotypic and functional properties. Our results provide an assessment of human T cell compartmentalization as a new baseline for understanding human adaptive immunity.
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“The preferred collagenase used by multiple research groups is collagenase IV [253, 256, 257, 267].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [253]
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“Trm do not express other putative activation markers, such as CD25, CD137, CD38, or HLA-DR [244, 253, 258, 264].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [253]
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In the citing paper
“Both CD8+ and CD4+ Trm have been identified in the human skin, lung, intestines, salivary glands, bone marrow, brain, spleen, tonsils, and lymph nodes [241, 244, 246, 253-259].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [253]
Experimental — accuracy not yet measuredIn the citing paper
“Seeding into tissues occurs in childhood, and the resident population persists throughout adulthood”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Sathaliyawala et al., 2013
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“Resident memory T cells in lungs, skin, and submucosal sites account for a large fraction of memory cells numbering more than 5 × 1010 cells in an individual.”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Sathaliyawala et al., 2013
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Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
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“The low proportion of CD8 Tcm cells compared to CD4 Tcm cells was not predicted from analysis of peripheral blood (Gattinoni et al., 2011; Sallusto et al., 1999) and is most striking when comparing whole body subset delineation as accomplished here.”
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“The low proportion of CD8 Tcm cells compared to CD4 Tcm cells was not predicted from analysis of peripheral blood (Gattinoni et al., 2011; Sallusto et al., 1999) and is most striking when comparing whole body subset delineation as accomplished here.”
Preferential Localization of Effector Memory Cells in Nonlymphoid Tissue
Masopust, D., Vezys, V., Marzo, A. L., & Lefrançois, L. (2001) · Science · doi:10.1126/science.1058867 · Cited by 1,952 · cited 1×
“CD45RO memory T cells are subdivided into two subsets: CCR7 ‘‘central memory’’ (Tcm) cells, which migrate to lymphoid tissue, and CCR7 ‘‘effector memory’’ (Tem) cells, which circulate to nonlymphoid sites (Masopust et al., 2001; Sallusto et al., 1999, 2004).”
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“CD69 memory T cells in lymphoid and mucosal sites were largely IL-7R (Figure 4B), indicative of a resting memory T cell phenotype, as IL-7R is downregulated on activated effector T cells (Dooms et al., 2007; Kaech et al., 2003; Paiardini et al., 2005; Seddiki et al., 2006).”
Ivanov, I. I., Frutos, R. D. L., Manel, N., Yoshinaga, K., Rifkin, D. B., Sartor, R. B., Finlay, B. B., & Littman, D. R. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.09.009 · Cited by 1,770
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“CD69 memory T cells in lymphoid and mucosal sites were largely IL-7R (Figure 4B), indicative of a resting memory T cell phenotype, as IL-7R is downregulated on activated effector T cells (Dooms et al., 2007; Kaech et al., 2003; Paiardini et al., 2005; Seddiki et al., 2006).”
Homeostasis of Naive and Memory T Cells
Surh, C. D., & Sprent, J. (2008) · Immunity · doi:10.1016/j.immuni.2008.11.002 · Cited by 1,193
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Metadata
- Authors
- Sathaliyawala, T., Kubota, M., Yudanin, N., Turner, D., Camp, P., Thome, J. J. C., Bickham, K. L., Lerner, H., Goldstein, M., Sykes, M., Kato, T., & Farber, D. L.
- Affiliations
- Columbia University Irving Medical Center (US)
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 38
- Issue
- 1
- Pages
- 187-197
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3557604
- OpenAlex
- W2082595913
- Cited by
- 848
- References
- 41
- Citations by year
- 2026: 33 · 2025: 39 · 2024: 50 · 2023: 54 · 2022: 74 · 2021: 77 · 2020: 78 · 2019: 96 · 2018: 95 · 2017: 75 · 2016: 69 · 2015: 47 · 2014: 40 · 2013: 20
- FWCI
- 14.97
- 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 Institutes of Health
- National Institute of Allergy and Infectious Diseases (RC1AI086164)
- National Center for Research Resources (S10RR027050)
- 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
- memory T cells, T cell compartmentalization, mucosal immunity, lymphoid tissue, effector memory T cells, central memory T cells, naive T cells, CD4+ T cells, CD8+ T cells, interleukin-2, interferon-gamma, CD69, T cell activation, tissue-resident T cells
- MeSH terms
- CD69 Antigens, Adolescent, Adult, Age Factors, Antigens, Differentiation, T-Lymphocyte, Female, Humans, Immunologic Memory, Male, Middle Aged, Mucous Membrane, Organ Specificity, Tissue Donors, CD4-Positive T-Lymphocytes, Antigens, CD, Immunophenotyping, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Lectins, C-Type, Integrin alpha Chains, Young Adult
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