Spatial Map of Human T Cell Compartmentalization and Maintenance over Decades of Life

Abstract

SUMMARY Mechanisms for human memory T cell differentiation and maintenance have largely been inferred from studies of peripheral blood, though the majority of T cells are found in lymphoid and mucosal sites. We present here a multidimensional, quantitative analysis of human T cell compartmentalization and maintenance over six decades of life in blood, lymphoid and mucosal tissues obtained from 56 individual organ donors. Our results reveal that the distribution and tissue residence of naïve, central and effector memory, and terminal effector subsets is contingent on both their differentiation state and tissue localization. Moreover, T cell homeostasis driven by cytokine or TCR-mediated signals is different in CD4+ or CD8+ T cell lineages, varies with their differentiation stage and tissue localization, and cannot be inferred from blood. Our data provide an unprecedented spatial and temporal map of human T cell compartmentalization and maintenance, supporting distinct pathways for human T cell fate determination and homeostasis.

Aging impacts CD103+CD8+ T cell presence and induction by dendritic cells in the genital tract

“…In contrast to the decline in cervix, we found that the percentage of TRMs increase in endometrial tissues of postmenopausal compared to premenopausal women and that this increase remains stable with postmenopausal aging. These findings were unexpected, since previous reports indicated no changes in TRM frequency with aging in other tissues, including the lung and intestines (Thome et al., 2014). Our findings suggest that differential mechanisms control the presence and the induction of TRMs in the FRT.…”

“…In humans, memory T cells with TRM characteristics have been identified at multiple mucosal surfaces including the lung, the intestines, and the FRT (Thome & Farber, 2015; Thome et al., 2014). In the FRT, more than 95% of T cells are effector memory (Saba et al., 2010; Yeaman et al., 1997), with a high proportion of T cells expressing CD103 in the vagina, endocervix (CX), ectocervix (ECX), and endometrium (EM) (Duluc et al., 2013; Moylan et al., 2016; Rodriguez‐Garcia et al., 2017).…”

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

“…In humans, Trm cells have been found in multiple organs, with elegant studies from Farber and colleagues tracking memory T‐cells in individuals of various ages. Human and mouse Trm cells share many characteristics, including CD69 expression and reduced expression of S1P receptor 1 37, 38. Similarly, CD4 Trm cells in skin are, like their mouse equivalent, mainly found in the dermis 39.…”

CTLA4-Ig in combination with FTY720 promotes allograft survival in sensitized recipients

“…-effector memory CD4 + and CD8 + T cells within the lymphoid compartments, including blood, accumulate rapidly with age (12). These high frequencies of heterologous memory T cells, if donor reactive, are postulated to play key roles in belataceptresistant rejection in both clinically sensitized as well as nonsensitized recipients.…”