IL-7 signaling in dendritic cells regulates CD4(+) T cell homeostatic proliferation and CD4(+) T cell niche size

Interleukin 7 (IL-7) and T cell receptor (TCR) signals have been proposed to be the primary drivers of homeostatic T cell proliferation. However, it is not known why CD4(+) T cells undergo less efficient homeostatic proliferation than CD8(+) T cells. Here we showed that systemic IL-7 concentrations rise during lymphopenia due to diminished IL-7 utilization, but that IL-7 signaling on IL-7Rα(+) dendritic cells (DCs) in lymphopenic settings paradoxically diminishes CD4(+) T cell homeostatic proliferation. This effect is mediated, at least in part, by IL-7-mediated downregulation of MHC class II expression on IL-7Rα(+) DCs. These results implicate IL-7Rα(+) DCs as regulators of the peripheral CD4(+) T cell niche, and indicate that IL-7 signals in DCs prevent uncontrolled CD4(+) T cell expansion in vivo.