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

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 γ 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. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.