Splenic stromal cells mediate IL-7 independent adult lymphoid tissue inducer cell survival

Eur J Immunol. 2010 Feb;40(2):359-65. doi: 10.1002/eji.200939776.

Abstract

Lymphoid tissue inducer cells (LTi) play an important role in the development of lymphoid tissue in embryos. Adult CD4(+)CD3(-) LTi-like cells present a similar phenotype and gene expression to their embryonic counterpart and have important roles in CD4(+) T-cell memory and lymphoid tissue recovery following viral infection. However, adult LTi-like cells are heterogeneous populations and the factors that regulate their survival and accumulation within secondary lymphoid organs remain unclear, in particular whether the T-zone stroma is involved. Here we report the identification and characterization of a distinct subset of podoplanin(+) murine splenic stromal cells that support adult LTi-like cell survival. We have identified and isolated CD45(-)podoplanin(+) stromal cell populations which have a similar but distinct phenotype to T-zone reticular cells in LN. CD45(-)podoplanin(+) fibroblast-like cells mediate LTi-like cell survival in vitro; surprisingly this was not dependent upon IL-7 as revealed through blocking Ab experiments and studies using LTi-like cells unable to respond to gamma chain cytokines. Our findings show that adult LTi-like cells require extrinsic signals from podoplanin(+) splenic stromal cells to survive and suggest that IL-7 is not necessary to mediate their survival in the adult spleen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Interleukin-7 / genetics
  • Interleukin-7 / metabolism*
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism
  • Lymphoid Tissue / cytology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / metabolism
  • Spleen / cytology
  • Stromal Cells / cytology
  • Stromal Cells / metabolism*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Time Factors

Substances

  • Gp38 protein, mouse
  • Interleukin-7
  • Membrane Glycoproteins
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain
  • Leukocyte Common Antigens
  • Ptprc protein, mouse