RESUMO
Interleukin-7 (IL-7) is considered a critical regulator of memory CD8+ T cell homeostasis, but this is primarily based on analysis of circulating and not tissue-resident memory (TRM) subsets. Furthermore, the cell-intrinsic requirement for IL-7 signaling during memory homeostasis has not been directly tested. Using inducible deletion, we found that Il7ra loss had only a modest effect on persistence of circulating memory and TRM subsets and that IL-7Rα was primarily required for normal basal proliferation. Loss of IL-15 signaling imposed heightened IL-7Rα dependence on memory CD8+ T cells, including TRM populations previously described as IL-15-independent. In the absence of IL-15 signaling, IL-7Rα was upregulated, and loss of IL-7Rα signaling reduced proliferation in response to IL-15, suggesting cross-regulation in memory CD8+ T cells. Thus, across subsets and tissues, IL-7 and IL-15 act in concert to support memory CD8+ T cells, conferring resilience to altered availability of either cytokine.
RESUMO
The thymus is an evolutionarily conserved organ that supports the development of T cells. Not only does the thymic environment support the rearrangement and expression of diverse T cell receptors but also provides a unique niche for the selection of appropriate T cell clones. Thymic selection ensures that the repertoire of available T cells is both useful (being MHC-restricted) and safe (being self-tolerant). The unique antigen-presentation features of the thymus ensure that the display of self-antigens is optimal to induce tolerance to all types of self-tissue. MHC class-specific functions of CD4+ T helper cells, CD8+ killer T cells and CD4+ regulatory T cells are also established in the thymus. Finally, the thymus provides signals for the development of several minor T cell subsets that promote immune and tissue homeostasis. This Review provides an introductory-level overview of our current understanding of the sophisticated thymic selection mechanisms that ensure T cells are useful and safe.
