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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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“After a certain stimulation, CD4 T cells undergo clonal expansion and differentiate into specific T cell subsets, such as T regulatory cells (Treg), T helper cells, which are closely associated with antitumor responses.(2,3) Previous study used a combinatorial approach to characterize the T cell receptor (TCR) profile…”
BackgroundT-cell lymphopenia in frequent volunteer platelet donors
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Roles of Menin in T cell differentiation and function: Current knowledge and perspectives
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“49,50 In our previous study, we showed that the defect in immunological memory CD4 + T cell formation is likely responsible for their lower production of anti-HBsAb after HB vaccination in NRs. 25 Considering the proven role of CXCR5 + CD8 + T cells in antibody production, which is in agreement…”
Non-equilibrium Cytokine Dynamics for Possible Therapeutic Intervention
Singh, M. K., Singh, M. S., & Singh, R. K. B. (2024) · Springer proceedings in physics · doi:10.1007/978-3-031-69134-8_4 · Cited by 1
Role of Regulatory Immune Cells in Tumour Microenvironment (TME)
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Evaluation of T memory cells in knee osteoarthritis patients
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“Confirming previous studies [15, 16, 35], ILCs developed several weeks before T cells could be detected in peripheral tissues (Figure S1F).”
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“The shorter telomeres in memory T cells than in naïve T cells reflect the formation of memory T cells through clonal expansion of naïve T cells (Kumar et al. 2018), a process that further shortens telomeres.”
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“T cells play a critical role in the adaptive immune response to tumors [8].”
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“As the prevailing immunological demands shift from infancy till adulthood, there is a corresponding change of roles in T cells ( 34 ).”
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Mini-review: Serum immunoglobulins and MASLD
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“HLA class I molecules present intracellular antigens to CD8 + T cells, while HLA class II molecules present extracellular antigens to CD4 + T cells [ 14 ].”
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“However, as cytotoxic T lymphocytes, CD8+ T cells play a crucial role in carrying out the anti-tumor immune response by directly destroying tumor cells (47, 48).”
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“This progressive deterioration reduces thymic output and compromises maintenance of the naive T-cells (Tn) compartment (8, 9).”
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“64,65 Our data suggest that Fcn promotes memory-like T cell programming, characterized by increased central and effector memory T cell populations and enhanced protection during subsequent Salmonella infection.”
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COVID-19 Tedavisinde Mezenkimal Kök Hücrelerin Potansiyel Kullanımı Üzerine Kapsamlı Bir İnceleme
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Self-reactive, innate-like T cells enhance cytotoxicity and immunosurveillance
Barton, B. E., Chau, C. H., & Figg, W. D. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.05.003 · Cited by 1
Effect of Age on the Clinicopathological Characteristics and Survival Outcomes of Thymoma Patients
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How Are Older Adults Different Than Other Adults for Infections?
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γδ T Cell-Mediated Immune Responses for Cancer Therapy: Special Focus on Breast Cancer
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The diverse landscape of memory T‐cell heterogeneity
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Inborn errors of immunity underlying defective T-cell memory
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“As key players in the immune system, these cells play a central role in adaptive immune response throughout life via interplay with other immune cells as well as non-immune cells (Kumar et al. 2018).”
Jiang, G., Neuber, B., Hückelhoven‐Krauss, A., Höpken, U. E., Ding, Y., Sedloev, D. N., Wang, L., Reichman, A., Eberhardt, F., Wermke, M., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031394 · Cited by 1
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“Considering that T cells expressing CTLA-4 protein migrate to the thymus for maturation, selection, and subsequent export to the periphery [32], our findings contribute to the concept of intrathymic pathogenesis in the initiation of the anti-AChR immune response in EOMG [33].”
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Glycogen nanoparticles for efficient mRNA transduction to T lymphocytes
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“…are essential immune response coordinators and effectors, helping to ∗ Author to whom any correspondence should be addressed. maintain immune homeostasis and playing an indispensable role in the surveillance and clearance of malignantly transformed or pathogen-infected cells and tumors [3, 4].”
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“Bone marrow-derived hematopoietic progenitor cells selectively migrate to the thymus, where they differentiate into precursor T cells [3].”
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GPU Acceleration of Conformational Stability Computation for CD4+ T-cell Epitope Prediction
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In silico design of Ebola virus Glycoprotein antigenic peptides as vaccine candidates
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Tissue-Specific Immunity in Osteoarticular Tuberculosis
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“%) in lymphoid sites with lower frequencies in mucosal tissues [34].”
Repeated Gonadotropin Administration Suppresses T Cell Development in the Mouse Thymus
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“As main players in the defense against pathogens, establishment of memory functions, immu-noregulation and screening for cancer cells, T cells regulate homeostasis in the body [213] and during ageing, T cells accumulate in the non-diabetic mouse pancreas [214].”
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Development of a novel CD3ε-specific human antibody for selective modulation of T cell activation
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Decoding T and B cell dynamics in inborn errors of immunity: insights into immune dysfunction
Caka, C., Sönmez, G., & Cağdaş, D. N. (2025) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2025.2564399 · Cited by 1
“Consequently, an increase in antigen-specific clones, clonal expansion, occurs [19,20].”
InfluentialAssessing the molecular fingerprint of T lymphocyte activation
Ramalhete, L., & Calado, C. R. C. (2019) · IEEE Portuguese Meeting on Bioengineering · doi:10.1109/enbeng.2019.8692471 · Cited by 1
“to the expansion, of specific T cell population, leading to an robust response to the immunological challenge [4].”
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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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