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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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“CD4+ T cells are crucial for combating infection and maintaining immune responses, homeostasis, and memory, and as such, are associated with several inflammatory and autoimmune diseases [29].”
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“By contrast, EBV-specific CD8 T-cell responses may be less effective in GALT because gut CD8 T cells are predominantly intra-epithelial and lamina propia CD8 Trm cells.(31,33) In addition, MS patients exhibit progressively less effective circulating CD8 Tm cell responses against EBV-infected B cells, related to a decr…”
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Protein O-GlcNAcylation in multiple immune cells and its therapeutic potential
Cai, H., Xiong, W., Zhu, H., Wang, Q., Liu, S., & Lu, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1209970 · Cited by 16
Bioengineering translational models of lymphoid tissues
Michaels, Y. S., Buchanan, C. F., Gjorevski, N., & Moisan, A. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-023-00101-0 · Cited by 16
Zhang, X., Ali, M. S., Pantuck, M. A., Yang, X., Lin, C.-R., Bahmed, K., Kośmider, B., & Tian, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1268078 · Cited by 15
“Additionally, the increased CD25 expression observed on activated CD8 T cells in our study contrasts with previous reports indicating minimal and indifferent CD25 expression on CD8 T cells in both COPD and control (42).”
ResultImmune Aging and Its Implication for Age-Related Disease Progression
Sato, Y. (2025) · Physiology · doi:10.1152/physiol.00051.2024 · Cited by 17
Shi, Z., Hu, C., Li, H., & Sun, C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26073234 · Cited by 16
“Th1 and Th2 cells are involved in cellular and humoral immunity, respectively, through the secretion of a variety of specific cytokines [155].”
A perspective on sepsis pathogenesis, biomarkers and diagnosis: A concise survey
Kundu, S., Tabassum, S., & Kumar, R. (2020) · Medical Devices & Sensors · doi:10.1002/mds3.10089 · Cited by 15
Lin, B., Wang, S., Yao, Y., Shen, Y., & Yang, H. (2021) · Oncology Letters · doi:10.3892/ol.2021.12759 · Cited by 15
Kim, W., Kim, G., Cho, H., & Choi, J. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13081134 · Cited by 15
“As immune cells, various types of T cells circulate or reside in the body and play an important role in the adaptive immune system [2].”
BackgroundExpert opinion on COVID-19 vaccination and the use of cladribine tablets in clinical practice
Rieckmann, P., Centonze, D., Giovannoni, G., Hua, L. H., Oreja‐Guevara, C., Selchen, D. H., Sørensen, P. S., Vermersch, P., Wiendl, H., Salloukh, H., et al. (2021) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864211058298 · Cited by 15
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Wang, C., Yuan, M., Gao, Y., Hou, R., Song, D., & Feng, Y. (2023) · Oncology Research and Treatment · doi:10.1159/000530161 · Cited by 14
T cell differentiation drives the negative selection of pathogenic mitochondrial DNA variants
Franklin, I. G., Milne, P., Childs, J., Boggan, R. M., Barrow, I., Lawless, C., Gorman, G. S., Ng, Y. S., Collin, M. P., Russell, O. M., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202302271 · Cited by 14
“T cell development involves a rigorous central tolerance process within the thymus, which involves rapid cell proliferation followed by death of unreactive/autoreactive cells (21).”
BackgroundRational design of polymer-based mRNA delivery systems for cancer treatment
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Shen, Z., Steeg, L. G. V., Patel, M. V., Rodríguez‐García, M., & Wira, C. R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1465124 · Cited by 14
“Understanding whether in fl ammation, recruitment, and/or retention contributes to the selective increase in TRMs with age in FRT tissue remains an area for further investigation.”
BackgroundInfluentialKometani, K., Yorimitsu, T., Jo, N., Yamaguchi, E., Kikuchi, O., Fukahori, M., Sawada, T., Tsujimoto, Y., Sunami, A., Li, M., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1455334 · Cited by 15
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Reduced immune-regulatory molecule expression on human colonic memory CD4 T cells in older adults
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“However, recent studies have underlined the inherent differences between circulating and tissue-resident T cells, including those that reside in the gut mucosa [14, 25], highlighting that care must be taken in simply extrapolating what we know about age effects on blood T cells to those in other tissues.”
BackgroundAlom, M. W., Shehab, M. N., Sujon, K. M., & Akter, F. (2021) · Informatics in Medicine Unlocked · doi:10.1016/j.imu.2021.100644 · Cited by 14
Jarvela, J. R., Moyer, M., Leahy, P. S., Bonfield, T. L., Fletcher, D., Mkono, W. N., Aung, H. L., Canaday, D. H., Dazard, J.-E., & Silver, R. F. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900230 · Cited by 14
Reddaway, J., & Brydges, N. M. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103567 · Cited by 17
“antigens are also recognised by T cell receptors on T lymphocytes: this induces T lymphocyte maturation and subsequent production of cytokines and recruitment of additional lymphocytes and macrophages (effector cells of the innate immune system) (Kumar et al., 2018; Reinherz and Schlossman, 1980).”
BackgroundCusenza, F., Davino, G., D’Alvano, T., Argentiero, A., Fainardi, V., Pisi, G., Principi, N., & Esposito, S. (2021) · Microorganisms · doi:10.3390/microorganisms9020330 · Cited by 14
“Moreover, in children, most naive T cells develop in the thymus, which is larger in childhood than in adulthood and undergoes involution with aging, while naive T cells self-renew exclusively in the peripheral blood in adults and elderly individuals [38].”
BackgroundSchoenberg, M. B., Han, Y., Li, X., Li, X., Bucher, J. N., Börner, N., Koch, D. T., Guba, M. O., Werner, J. M., & Bazhin, A. V. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12020718 · Cited by 13
“This does not only lead to immune activating but in some cases conversely to immunosuppressive effects (T regulatory cells) [9].”
BackgroundTissue-resident memory CD8+ T cells: master deciphers of the hepatic environment
Romero, D. B., Finney, G. E., Dudek, M., & Pallett, L. J. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01118-z · Cited by 13
“These phenotypic markers for CD8 + T RM cells, along with key transcription factors regulating their function, are highlighted and further explained in Table 2 and reviewed elsewhere in greater detail 2,58,59 .”
Treatment Response Biomarkers in Asthma and COPD
Meteran, H., Sivapalan, P., & Jensen, J. S. (2021) · Diagnostics · doi:10.3390/diagnostics11091668 · Cited by 13
“The T-lymphocytes consist mostly of TH1, TH17, and cytotoxic T cells [4].”
BackgroundShen, D.-S., Chang, Y., Liang, Y., Chen, K.-H., & Zhu, X. (2021) · Cancer Management and Research · doi:10.2147/cmar.s334094 · Cited by 13
Wang, K., Gu, Y., Ni, J., Zhang, H., Wang, Y., Zhang, Y., Sun, X., Xu, T., Mao, W., & Peng, B. (2022) · Bioengineered · doi:10.1080/21655979.2022.2060787 · Cited by 13
“T lymphocytes occupy an irreplaceable position in the human immune system, and they can influence the development of many diseases, such as autoimmunity, by regulating the body’s immune responses[11].”
BackgroundHermawan, A., Damai, F. I., Martin, L., Chrisdianto, M., Julianto, N. M., Pramanda, I. T., & Gustiananda, M. (2022) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-022-10467-1 · Cited by 13
Specificity and function of T cell subset identities using single‐cell sequencing
Liu, X., Zhu, Z., & Wang, X. (2023) · Clinical and Translational Discovery · doi:10.1002/ctd2.199 · Cited by 15
Clonal Neoantigen: Emerging “Mechanism-based” Biomarker of Immunotherapy Response
Nemunaitis, J. J., Stanbery, L., Willoughby, D., Bognar, E., Brun, S., Walter, A., Monk, B. J., Rocconi, R. P., Choucair, K., & Coleman, R. L. (2023) · Cancers · doi:10.3390/cancers15235616 · Cited by 14
“Ad-ditionally almost “pre-ventative” stage attempting to provide durability to the anti-cancer response [56,57].”
BackgroundHi-C, a chromatin 3D structure technique advancing the functional genomics of immune cells
Liu, R., Xu, R., Yan, S., Li, P., Jia, C., Sun, H., Sheng, K., Wang, Y., Zhang, Q., Guo, J., et al. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1377238 · Cited by 15
“The development process of T cells mainly involves the stages of pro-T cells, CD4 − CD8-double-negative (DN) thymocytes, CD4 + CD8 + double-positive (DP) thymocytes, CD8 + single-positive T cells, and CD4 + single-positive T cells (Kumar et al., 2018).”
BackgroundCD4+ T-cell subsets are associated with chronic stress effects in newly diagnosed anxiety disorders
Dai, B., Li, T., Cao, J., Zhao, X., Jiang, Y., Shi, L., & Wei, J. (2024) · Neurobiology of Stress · doi:10.1016/j.ynstr.2024.100661 · Cited by 13
“…antigen stimulation, co-stimulatory molecule activation, and cytokine stimulation, naïve CD4 + T cells undergo proliferation and differentiation to form different effector cell subsets and memory cell pools, thereby exerting effector functions and maintaining immune homeostasis(Kumar et al., 2018).”
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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