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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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“…shown increased T cell infiltration in the salivary glands of patients with Sjögren’s syndrome, primarily consisting of CD4 + and CD8 + T cells [33,34], with the latter rarely undergoing local proliferation during disease progression but being readily recruited and differentiated from peripheral…”
Cancer-associated fibroblasts: enablers of tumor drug resistance
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“It is known that the adaptive immune system begins to mature at that time(Adkins et al., 2004), while T cells play important roles in the process of cellular immunity(Kumar et al., 2018; Lee et al., 2020; Mantovani et al., 2011).”
Xue, Z., Wang, Z., Liu, D., Li, B., Sun, Z., Zhao, J., Li, H., Wang, X., & Sun, Y. (2025) · Immunologic Research · doi:10.1007/s12026-025-09628-3 · Cited by 4
“IL-2 promotes NK cell survival and expansion through the JAK3-STAT5 pathway [22, 23].”
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“The increase in the late-stage effector lymphocyte populations are usually seen as a result of the continuous attempts of the immune system to control CMV reactivation and are part of the success of this operation [46, 47].”
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“While the functions of B cells and antibodies are mostly for ridding the body of soluble/free toxins, viruses and bacteria [1], the functions of T cells are for monitoring the status of host cells for signs of viral infection and malignant transformation [2,3].”
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“Through interactions with a diverse array of immune cells, T cells amplify the production of cytokines and chemokines, shaping the immune microenvironment of the GN [6].”
Phenotypes and mechanisms of dysfunctional cardiac T-lymphocytes in dilated cardiomyopathy patients
Angelotti, A., Ponnusamy, T., Kumar, D. V., Passarelli, G. V., Malysz, J., Mahesh, B., Soleimani, B., Bradley, E. A., & Bansal, S. S. (2025) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2025.12.011 · Cited by 4
“Human T-cells are largely comprised of non-tissue resident effector or central memory (TEM or TCM, respectively) or tissue-resident memory (TRM) T-cells with distinct phenotypes and surface expression patterns [46].”
Ye, X., Huang, W., Chen, S., Huang, F. P., & He, Y. (2026) · Stem Cell Research & Therapy · doi:10.1186/s13287-026-04901-0 · Cited by 4
“Originating in the bone marrow and maturing within the thymus, T lymphocytes are a cornerstone of the human immune system [83].”
Autoimmune skin disease pathogenesis: a chronological immune cascade and multi-hit model
Chen, J., Yin, H., Li, S., & Li, C. (2026) · Immunity & Inflammation · doi:10.1007/s44466-025-00017-x · Cited by 5
“In healthy skin, T RM constitute approximately 20% − 60% of memory T cells, but nearly all the CD8 + T cells in viti-ligo lesional skin adopt the features of T RM [219–221].”
Serglycin Drives LAG3+ Treg Differentiation and Immunosuppression in Gastric Cancer
Wang, Q., Xu, P., Chen, J., Yang, S., Li, X., Wang, Y., Hua, H. J., Ping, X., Shen, J., & Shen, L. (2026) · Cancer Research · doi:10.1158/0008-5472.can-25-3071 · Cited by 4
The immune landscape of uterine fibroids as determined by mass cytometry
Boos, D., Chuang, T., Abbasi, A., Luzzi, A., & Khorram, O. (2024) · F&S Science · doi:10.1016/j.xfss.2024.06.004 · Cited by 6
More severe parotid gland histopathology in paediatric-onset than in adult-onset Sjögren’s disease
Legger, G. E., Nakshbandi, U., van Ginkel, M. S., Liefers, S. C., de Wolff, L., Stel, A. J., Armbrust, W., Spijkervet, F. K. L., Vissink, A., Arends, S., et al. (2024) · RMD Open · doi:10.1136/rmdopen-2024-004201 · Cited by 4
“Our advice is to take the histopathological findings of the salivary gland biopsies into account when evaluating the disease activity in patients with pedSjD and to consider adjusting treatment strategies according to these findings.”
MethodEllsworth, S. G., Ross, A., Shiue, K., Murthy, P., Byrne-Steele, M. L., Patel, R. B., Zellars, R. C., Kong, F., Miller, A., Russ, K. A., et al. (2024) · Radiation Research · doi:10.1667/rade-24-00010.1 · Cited by 4
“T-cell selection, which eliminates both insufficiently and excessively self-reactive T cells, results in further individualization of the immune repertoire ( 7 ).”
Targeting T-Cell Activation for Malaria Immunotherapy: Scoping Review
Gustifante, B. N., Khairani, S., Fauziah, N., Riswari, S. F., & Berbudi, A. (2025) · Pathogens · doi:10.3390/pathogens14010071 · Cited by 4
“However, the complexity of immune evasion strategies employed by Plasmodium necessitates further research into enhancing T-cell activation and sustaining their efficacy [9,10].”
Origins of T‐cell‐mediated autoimmunity in acquired aplastic anaemia
Enache, A., Carty, S. A., & Babushok, D. V. (2025) · British Journal of Haematology · doi:10.1111/bjh.19993 · Cited by 5
“83 However, practically, peripheral blood (PB) is more accessible and more readily available tissue, and PB T cells have been commonly used in AA studies in lieu of BM samples.”
Kim, G.-D., Yoo, S. H., Song, J. H., Lim, K. M., Lim, E. Y., Yoo, J. Y., Lee, D.-K., Cho, Y.-B., Yu, H.-J., Lee, S., et al. (2024) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2411.11006 · Cited by 5
Han, J. W., & Shin, E. (2025) · Gut and Liver · doi:10.5009/gnl240366 · Cited by 5
Yu, X., Ding, J., He, Y., Wei, S., Chen, X., Luo, Q., Zhang, Y., Qian, C., Wang, J., Hu, M., et al. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.101677 · Cited by 4
“Meanwhile, T lymphocytes are essential for adaptive immune responses and the maintenance of immune homeostasis [52].”
Role of the neurotransmitter-receptor pathway in T-cell tumor immunology and cancer immunotherapy
Fan, M., & Zhao, X. (2025) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2025216 · Cited by 4
“T cells are central effectors of the adaptive immune system and are essential for maintaining immune homeostasis and orchestrating antitumor immune responses [1,2].”
Xu, H., Lee, H., Schmitz, R., Shaw, B. I., Li, S., & Kirk, A. D. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16625 · Cited by 4
Naïve T cells may be key to the low mortality of children with COVID‐19
Zhang, W., Zhou, Y., & Kang, Y. (2022) · Journal of Evidence-Based Medicine · doi:10.1111/jebm.12454 · Cited by 4
Protective effects of Korean Red Ginseng against toxicity of endocrine-disrupting chemicals
Jung, E., Lee, S. H., & Lee, G. (2022) · Journal of Ginseng Research · doi:10.1016/j.jgr.2022.11.007 · Cited by 4
Jian, X., Zhang, Y. L., Zhao, J., Zhao, Z., Lu, M., & Xie, L. (2023) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2023.01.038 · Cited by 4
“In general, the recognition of antigens by T cells activates their proliferation and/or phenotypic changes, leading to alteration of TCR repertoire [30,31].”
Raman Spectroscopy Profiling of Splenic T-Cells in Sepsis and Endotoxemia in Mice
Osadare, I. E., Xiong, L., Rubio, I., Neugebauer, U., Press, A. T., Ramoji, A., & Popp, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512027 · Cited by 4
Gene Editing and Gene Therapy in Oncology
Wierson, W. A., Abel, A. M., Siegler, E. L., Ekker, S. C., Johannes, C. M., Kenderian, S. S., & Mochel, J. P. (2023) · CABI eBooks · doi:10.1079/9781789245820.0009 · Cited by 3
Pan, T., Ding, P., Huang, A., Tang, B., Song, K., Sun, G., Wu, Y., Yang, S., Chen, X., Wang, D., et al. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002807 · Cited by 4
Zhang, D., Jia, M., Wang, C., Li, Y., Ma, C., Zhu, G., Ma, R., Wen, D., Jia, X., Xu, G., et al. (2023) · Experimental Biology and Medicine · doi:10.1177/15353702231198083 · Cited by 4
“33 However, in our study, to ensure the success of the operation on ETM/ES mice, adult mice (10–24 weeks) were selected in the first part of the experiment.”
MethodDysregulated metal ion homeostasis underscores non-canonical function of CD8+ T cell during COVID-19
Khare, K., Chattopadhyay, P., Devi, P., Mehta, P., Raina, A., Liu, C. S. C., Tardalkar, K., Joshi, M. G., & Pandey, R. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1282390 · Cited by 4
“Subsequently, a subset of these activated cells undergoes maturation, giving rise to various memory subsets, including central memory T cells, effector memory T cells and tissue-resident memory T cells (12).”
Background11-deoxycortisol positively correlates with T cell immune traits in physiological conditions
Peng, C., Jiang, X., Jaeger, M., van Houten, P., van Herwaarden, A. E., Koeken, V. A. C. M., Moorlag, S. J. C. F. M., Mourits, V. P., Lemmers, H., Dijkstra, H., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104935 · Cited by 5
“29,30 T cell proliferation requires the co-stimulation of TCR-CD3/CD28 complex by antigen-presenting cells, hence we used CD3/CD28 dynabeads to mirror this stimulation.”
MethodThe importance of Ca2+ microdomains for the adaptive immune response
Diercks, B. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2024.119710 · Cited by 6
Human T cell development and aging: Remodeling throughout the lifespan
Mao, L., Feng, Q., Luo, O. J., Chen, G., & Leng, X. S. (2024) · Aging Research · doi:10.26599/agr.2024.9340021 · Cited by 5
Fang, Y., Liu, Y., Dong, Z., Zhao, X., Zhang, M., Zheng, Y., Yang, C., Wang, Y., Liu, N., Yan, P., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-75180-z · Cited by 4
“TILs participate in the formation of the tumour microenvironment, regulate local tumour immunity and are regarded as the most important part of the tumour immune microenvironment 22,23 .”
BackgroundFrom non-coding to coding: The importance of long non-coding RNA translation in de novo gene birth
Shiraishi, T., & Matsumoto, A. (2024) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2024.130747 · Cited by 6
Takeda, Y., Ezoe, Y., Iwamae, Y., Kimura, T., Tomitsuka, K., Koyama, S., Imoto, K., Morishima, H., Nogami, S., & Yamauchi, K. (2025) · Journal of Oral and Maxillofacial Surgery Medicine and Pathology · doi:10.1016/j.ajoms.2025.02.006 · Cited by 4
Tiemessen, C. T. (2025) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000918 · Cited by 4
“Early-life immune responses are more regulatory and less inflammatory, preventing overreactions but limiting the ability to effectively memory and functional capability [4,5].”
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
“…T cells (T CM ) home to and predominate in lymphoid tissue, effector memory T cells (T EM ) home to and predominate in non-lymphoid tissues, and effector memory T cells re-expressing CD45RA (T EMRA ) predominate in the circulation (Gattinoni et al., 2011; Kumar et al., 2018; Sallusto et al., 1999).”
The Progress of Immune Cells-induced Inflammatory Response in Gout
Liu, J., Liu, G., Chu, T., Wu, Y., Yang, L. Z., & Fang, W. (2025) · Current Pharmaceutical Design · doi:10.2174/0113816128369016250306050522 · Cited by 4
Huo, M., Liu, H., Chen, S., Xiu, L., Yu, X. L., & Zhong, G. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1557717 · Cited by 4
“…to the peripheral blood, resulting in marrow progenitor cells lacking CD4 and CD8 co-expressed receptors differentiate into CD4 (+) or CD8 (+) single positive (SP) cells after dual selection, and then are transported to the periphery to perform effective immune functions (Kumar et al., 2018).”
Hu, Y., Li, H., Wang, X., Duan, X., Zhang, Y., Wen, B., Dong, S., Yan, Z., Fan, Y., & Jing, Y. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114812 · Cited by 4
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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