Splenic stromal cells mediate IL-7 independent adult lymphoid tissue inducer cell survival.
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.
Hou
Tie Zheng
TZ
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.
Mustafa
Mohammad Z
MZ
Flavell
Sarah J
SJ
Barrington
Fern
F
Jenkinson
Eric J
EJ
Anderson
Graham
G
Lane
Peter J L
PJ
Withers
David R
DR
Buckley
Christopher D
CD
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
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