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

Abstract

In an anti-glomerular basement membrane (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 (days 17-25). When examined at day 45, both histopathology and blood urea nitrogen/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. © 2014 International Society of Nephrology.