CD8+ regulatory T cells induced by T cell vaccination protect against autoimmune nephritis
Autoreactive T cells play a pivotal role in the pathogenesis of autoimmune kidney disease. T cell vaccination (TCV)may limit autoimmune disease and induce CD8+ regulatory T cells (Tregs).We usedHeymann nephritis (HN), a ratmodel of humanmembranous nephritis, to study the effects ofTCV on autoimmune kidney disease. We harvestedCD4+ T cells fromrenal tubular antigen (Fx1A) -immunized rats and activated these cells in vitro to express theMHCClass IbmoleculeQa-1. Vaccination of Lewis ratswith these autoreactive Fx1A-induced T cells protected against HN, whereas control-primed T cells did not. Rats that underwent TCV had lower levels of proteinuria and serum creatinine and significantly less glomerulosclerosis, tubular damage, and interstitial infiltrates. Furthermore, these rats expressed less IFN-g and IL-6 in splenocytes, whereas the numbers of Tregs and the expression of Foxp3 were unchanged. In vitro cytotoxicity assays showed CD8+ T cell-mediated elimination of Qa-1–expressing CD4+ T cells. In vivo, TCV abrogated the increase inQa-1–expressing CXCR5+ TFH cells observed in HN compared with controls. Taken together, these results suggest that TCV protects against autoimmune kidney disease by targeting Qa-1–expressing autoreactive CD4+ cells.