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

Julie Robertson¹  Marvin L. Meistrich¹  Cindy Zhou¹  Ramesh C. Tailor  and¹  Jean Wu¹  Connie C. Y. Weng¹  Ya-Huan Lou¹ 

[1] Department of Diagnostic Sciences, DB, University of Texas Health Science Center at Houston, and  Departments of Experimental Radiation Oncology and Radiation Physics, M.D. Anderson Cancer Center, University of Texas, Houston, Texas, USA

关键词: autoimmunity;    apoptosis;    tolerance;    kidney;   

DOI  :  10.1189/jlb.0310133

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 infiltration of the cells into glomeruli, suggesting that the cells may also induce T cell apoptosis in vivo. A potential role of this CD8αα+ DC-like population in peripheral immune tolerance and/or termination of autoimmune inflammation was discussed.

【 授权许可】

Unknown