title: 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 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.
authors: School of Immunity and Infection, MRC Centre for Immune Regulation, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors: Tie Zheng
authors: TZ
authors: Hou
authors: Mohammad Z
authors: MZ
authors: Mustafa
authors: Sarah J
authors: SJ
authors: Flavell
authors: Fern
authors: F
authors: Barrington
authors: Eric J
authors: EJ
authors: Jenkinson
authors: Graham
authors: G
authors: Anderson
authors: Peter J L
authors: PJ
authors: Lane
authors: David R
authors: DR
authors: Withers
authors: Christopher D
authors: CD
authors: Buckley
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D000098853:Podoplanin
chemical_list: D015851:Interleukin-7; D017493:Leukocyte Common Antigens; D008562:Membrane Glycoproteins; D020395:Receptors, Interleukin-7; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C415350:interleukin-7 receptor, alpha chain; C516770:Ptprc protein, mouse