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

Guimond M., Veenstra R. G., Grindler D. J., Zhang H., Cui Y., Murphy R. D., ...More

NATURE IMMUNOLOGY, vol.10, no.2, pp.149-157, 2009 (SCI-Expanded) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 10 Issue: 2
  • Publication Date: 2009
  • Doi Number: 10.1038/ni.1695
  • Journal Name: NATURE IMMUNOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.149-157
  • Acibadem Mehmet Ali Aydinlar University Affiliated: No

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-alpha-positive (IL-7R alpha(+)) 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-7R alpha(+) DCs. Our results indicate that IL-7R alpha(+) 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.