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Human T Cell Development, Localization, and Function throughout Life
Open accessAbstract
Throughout life, T cells coordinate multiple aspects of adaptive immunity, including responses to pathogens, allergens, and tumors. In mouse models, the role of T cells is studied in the context of a specific type of pathogen, antigen, or disease condition over a limited time frame, whereas in humans, T cells control multiple insults simultaneously throughout the body and maintain immune homeostasis over decades. In this review, we discuss how human T cells develop and provide essential immune protection at different life stages and highlight tissue localization and subset delineation as key determinants of the T cell functional role in immune responses. We also discuss how anatomic compartments undergo distinct age-associated changes in T cell subset composition and function over a lifetime. It is important to consider age and tissue influences on human T cells when developing targeted strategies to modulate T cell-mediated immunity in vaccines and immunotherapies.
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“Younger patients may be more capable of mounting the interferondriven, anti-viral innate response critical to GTAU and developing robust adaptive immunity compared to adults and the elderly (Kumar et al., 2018; Yoshida et al., 2022).”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Kumar et al., 2018
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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 [264]
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“Tregs are present throughout the human body and their abundance in circulation and tissues is age dependent [264, 359].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [264]
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“An additional layer of complexity is added by the different memory CD4+ T cell subsets generated during the primary immune response [3,5].”
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“CD45RACCR7 cells represent naive T cells, CD45RA(2)CCR7 cells represent central memoryTcells,CD45RA(2)CCR7(2)cells representT-effector/ effector memory T cells, and CD45RACCR7(2) cells represent terminally differentiated effector memory CD45RA T cells (TEMRAs) (45, 46).”
BackgroundImmunology of SARS-CoV-2 infection in children
Chou, J. S., Thomas, P. G., & Randolph, A. G. (2022) · Nature Immunology · doi:10.1038/s41590-021-01123-9 · Cited by 176
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“The thymus is the primary site of T cell differentiation into which T progenitor cells migrate from the bone marrow and undergo TCR rearrangement, giving rise to the two major subtypes of T cells: helper and regulatory (CD4) or cytotoxic (CD8) T cells (81).”
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“DISCUSSION T cells are increasingly appreciated for their plasticity in adapting to tissue environments, allowing them to persist and orchestrate coordinated tissue-specific immune surveillance and other homeostatic functions (15).”
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“In humans, populations of TRMs constitute the majority of T cells throughout the body and are present in constant frequencies over many decades of human life (Kumar et al., 2018a; Senda et al., 2019; Thome et al., 2014).”
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Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span
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“Moreover, although T lymphocytes coordinate and maintain immunological memory and self-tolerance, they have also been linked to inflammatory and autoimmune diseases (3).”
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“In parallel to the reduction in the number of naïve T cells, memory cells gradually occupy the T-cell compartment (Elyahu et al., 2019; Kumar et al., 2018; Saule et al., 2006; Thome et al., 2014), a shift that is generally evident as a reduced expression of naïve cell markers, such as CD62 L (in mice), Ccr7 (in mice a…”
Aging, inflammaging and immunosenescence as risk factors of severe COVID-19
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“These include, T helper (Th)1, that protect intracellular pathogens Th2, and Th17 which target extracellular pathogens, regulatory T cells which help maintain self-tolerance and the follicular helper T cells (TFH) that assist B cells for antibody production [162].”
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Metadata
- Authors
- Kumar, B. V., Connors, T. J., & Farber, D. L.
- Affiliations
- Columbia University Irving Medical Center (US)
- ORCID
- Connors, Thomas J.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 48
- Issue
- 2
- Pages
- 202-213
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC5826622
- OpenAlex
- W2789026035
- Cited by
- 1,257
- References
- 132
- Citations by year
- 2026: 100 · 2025: 181 · 2024: 213 · 2023: 207 · 2022: 233 · 2021: 171 · 2020: 85 · 2019: 47 · 2018: 19
- FWCI
- 8.30
- 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
- NIH (AI106697, AI128949)
- 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
- T cell development, T cell localization, T cell subsets, immunosenescence, tissue localization, immune homeostasis, adaptive immunity, age-related changes, T cell immunity, vaccines, immunotherapy
- MeSH terms
- Animals, Humans, Immunologic Memory, T-Lymphocytes, Tissue Distribution, T-Lymphocyte Subsets, Lymphopoiesis, T-Lymphocytes, Regulatory, Adaptive Immunity
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