Peripheral blood CD8αα(+)CD11c(+)MHC(−)II(+)CD3- cells attenuate autoimmune glomerulonephritis in rats

In an anti-GBM glomerulonephritis (GN) model, GN-resistant Lewis rats naturally recover from early glomerular inflammation. Here we investigated recovery mechanisms for development of a potential immunotherapy for autoimmune GN. Our previous studies suggested that glomeruli-infiltrating leukocytes with a phenotype of CD8αα(+)CD11c(+)MHC(−)II(+)CD3(−) (GIL CD8αα(+) cells) were responsible for recovery through induction of T cell apoptosis. Now, we identified peripheral blood CD8αα(+)CD11c(+)MHC(−)II(+)CD3(−) cells (PBMC CD8αα(+)CD3(−) cells), which shared 9 markers with GIL CD8αα(+) cells. Upon incubation, PBMC CD8αα(+)CD3(−) cells displayed a morphology resembling that of dendritic cells. Similar to GIL CD8αα(+) cells, PBMC CD8αα(+)CD3(−) cells were capable of inducing T cell apoptosis in vitro. Hence, PBMC CD8αα(+)CD3(−) cells were likely the precursor of GIL CD8αα(+) cells. We next tested their potential in vivo function. PBMC CD8αα(+)CD3(−) cells were able to infiltrate inflamed but not normal glomeruli. Isolated PBMC CD8αα(+)CD3(−) cells of Lewis rats were transferred into GN-prone Wistar Kyoto rats at early inflammatory stage (day 17–25). When examined at day 45, both histopathology and BUN/serum creatinine level showed significantly attenuated GN in 80% of cell recipient Wistar Kyoto rats. Separate experiments verified infiltration of transferred Lewis PBMC CD8αα(+)CD3(−) into the glomeruli, accompanied with apoptotic CD4(+) T cells in the glomeruli of the recipient Wistar Kyoto rats. Thus, PBMC CD8αα(+)CD3(−) cells of Lewis rats were able to terminate ongoing autoimmune inflammation in the glomeruli.