By contrast, the corresponding blood samples were low in T cells, but high in other immune cells called monocytes, which were displaying unusual patterns of cell-surface receptors. Mouse studies have ...also shown that, for site-specific viruses such as influenza or human papillomavirus, immunological memory is maintained by dedicated sets of memory T cells at the relevant site. After clinical teams obtain the person's organs for transplantation, our surgeon collects tissues for research - including the intestines, lungs, many lymph nodes, the thymus, spleen, bone marrow, skin, tonsils and salivary glands - and brings everything directly back to the laboratory for processing and sample storage. Technological advances mean that RNA transcripts, protein content and gene modifications can be pinpointed even for single cells.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
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.
► Human memory CD4+ and CD8+ T cell subsets exhibit tissue-specific compartmentalization ► CD69 is constitutively upregulated by all tissue-resident but not circulating T cells ► Memory CD4+ T cells producing IL-2 are the majority subset throughout the human body
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The thymus is a primary lymphoid organ essential for the development of T lymphocytes, which orchestrate adaptive immune responses. T-cell development in the thymus is spatially regulated; key ...checkpoints in T-cell maturation and selection occur in cortical and medullary regions to eliminate self-reactive T cells, establish central tolerance, and export naïve T cells to the periphery with the potential to recognize diverse pathogens. Thymic output is also temporally regulated due to age-related involution of the thymus accompanied by loss of epithelial cells. This review discusses the structural and age-related control of thymus function in humans.
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.
Recent studies of human T cells in diverse tissue sites have revealed that the functional role of T cells is closely linked to the anatomical location, subset, and developmental stage. Kumar et al. review these advances and highlight human-specific aspects of T cell immunity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tissue-resident memory T cells (TRM) represent a heterogeneous T cell population with the functionality of both effector and memory T cells. TRM express residence gene signatures. This feature allows ...them to traffic to, reside in, and potentially patrol peripheral tissues, thereby enforcing an efficient long-term immune-protective role. Recent studies have revealed TRM involvement in tumor immune responses. TRM tumor infiltration correlates with enhanced response to current immunotherapy and is often associated with favorable clinical outcome in patients with cancer. Thus, targeting TRM may lead to enhanced cancer immunotherapy efficacy. Here, we review and discuss recent advances on the nature of TRM in the context of tumor immunity and immunotherapy.
This Pillars of Immunology article is a commentary on the following two seminal articles: “Visualizing the generation of memory CD4 T cells in the whole body,” an article written by R. L. Reinhardt, ...A. Khoruts, R. Merica, T. Zell, and M. K. Jenkins, and published in Nature, in 2001. https://www.nature.com/articles/35065111, and “Protection from respiratory virus infections can be mediated by memory CD4 T cells that persist in the lungs,” by R. J. Hogan, W. Zhong, E. J. Usherwood, T. Cookenham, A. D. Roberts, and D. L. Woodland, and published in the Journal of Experimental Medicine, in 2001. https://doi.org/10.1084/jem.193.8.981.
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