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

M Guimond, RG Veenstra, DJ Grindler, H Zhang… - Nature …, 2009 - nature.com
M Guimond, RG Veenstra, DJ Grindler, H Zhang, Y Cui, RD Murphy, SY Kim, R Na…
Nature immunology, 2009nature.com
Abstract 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 …
Abstract
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.
nature.com