Identification of a bone marrow-derived CD8αα+ dendritic cell-like population in inflamed autoimmune target tissue with capability of inducing T cell apoptosis.

Journal of Leukocyte Biology
Jean WuYa-Huan Lou

Abstract

DCs play critical roles in promotion of autoimmunity or immune tolerance as potent APCs. In our anti-GBM GN model, WKY rats develop severe T cell-mediated glomerular inflammation followed by fibrosis. A DC-like cell population (CD8αα(+)CD11c(+)MHC-II(+)ED1(-)) was identified in the inflamed glomeruli. Chimera experiments demonstrated that the CD8αα(+) cells were derived from BM. The CD8αα(+) cells infiltrated glomeruli at a late stage (Days 28-35), coincident with a rapid decline in glomerular inflammation before fibrosis. The CD8αα(+) cells isolated from inflamed glomeruli were able to migrate rapidly from the bloodstream into inflamed glomeruli but not into normal glomeruli, suggesting that the migration was triggered by local inflammation. Despite high-level expression of surface and cellular MHC class II molecules, in vitro experiments showed that this CD8αα(+) DC-like cell induced apoptosis but not proliferation in antigen-specific CD4(+) T cells from T cell lines or freshly isolated from lymph nodes; they were not able to do so in the absence of antigens, suggesting induction of apoptosis was antigen-specific. Furthermore, apoptotic T cells were detected in a large number in the glomeruli at Day 32, coincident with the in...Continue Reading

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Citations

Apr 18, 2014·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·A Richard Kitching
May 3, 2014·Kidney International·Kevin J Woollard, Charles D Pusey
Nov 2, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jean WuYahuan Lou
Feb 22, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sun-Sang J SungJessica R Lawler
Nov 3, 2010·Journal of Leukocyte Biology·Sun-sang J Sung, Warren K Bolton
Jan 27, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jean WuYahuan Lou

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