Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells

Nat Immunol. 2007 Nov;8(11):1255-65. doi: 10.1038/ni1513. Epub 2007 Sep 23.

Abstract

Interleukin 7 is essential for the survival of naive T lymphocytes. Despite its importance, its cellular source in the periphery remains poorly defined. Here we report a critical function for lymph node access in T cell homeostasis and identify T zone fibroblastic reticular cells in these organs as the main source of interleukin 7. In vitro, T zone fibroblastic reticular cells were able to prevent the death of naive T lymphocytes but not of B lymphocytes by secreting interleukin 7 and the CCR7 ligand CCL19. Using gene-targeted mice, we demonstrate a nonredundant function for CCL19 in T cell homeostasis. Our data suggest that lymph nodes and T zone fibroblastic reticular cells have a key function in naive CD4(+) and CD8(+) T cell homeostasis by providing a limited reservoir of survival factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Survival
  • Chemokine CCL19 / immunology
  • Chemokine CCL19 / metabolism
  • Fibroblasts / metabolism*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression
  • Homeostasis / immunology*
  • In Situ Hybridization
  • Interleukin-7 / biosynthesis
  • Lymph Nodes / cytology*
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology

Substances

  • Chemokine CCL19
  • Interleukin-7
  • RNA, Messenger