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