Title

CD8+ regulatory T cells induced by T cell vaccination protect against autoimmune nephritis

RIS ID

59311

Publication Details

Wang, Y. Min., Zhang, G. Yu., Hu, M., Polhill, T., Sawyer, A., Zhou, J. Jianheng., Saito, M., Watson, D., Wu, H., Wang, Y., Wang, X. Maggie., Wang, Y., Harris, D. C. H. & Alexander, S. I. (2012). CD8+ regulatory T cells induced by T cell vaccination protect against autoimmune nephritis. Journal of the American Society of Nephrology, 23 (6), 1058-1067.

Abstract

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.

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Link to publisher version (DOI)

http://dx.doi.org/10.1681/ASN.2011090914