Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells

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Abstract
Compared with naive CD8+ T cells, naive CD4+ T cells undergo inefficient homeostatic proliferation. Mackall and colleagues now attribute this difference to interleukin 7–mediated suppression of the expression of MHC class II on dendritic cells. Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4+ T cells undergo less-efficient homeostatic proliferation than CD8+ T cells do. Here we show that systemic IL-7 concentrations increased during lymphopenia because of diminished use of IL-7 but that IL-7 signaling on IL-7 receptor-α–positive (IL-7Rα+) dendritic cells (DCs) in lymphopenic settings paradoxically diminished the homeostatic proliferation of CD4+ T cells. This effect was mediated at least in part by IL-7-mediated downregulation of the expression of major histocompatibility complex class II on IL-7Rα+ DCs. Our results indicate that IL-7Rα+ DCs are regulators of the peripheral CD4+ T cell niche and that IL-7 signals in DCs prevent uncontrolled CD4+ T cell population expansion in vivo.