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

Yuan Min Wang, Geoff Yu Zhang, Min Hu, Tania Polhill, Andrew Sawyer, Jimmy Jianheng Zhou, Mitsuru Saito, Debbie Watson, Huiling Wu, Ya Wang, Xin Maggie Wang, Yiping Wang, David C. H. Harris, Stephen I. Alexander*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 used Heymann nephritis (HN), a rat model of human membranous nephritis, to study the effects of TCV on autoimmune kidney disease. We harvested CD4+ T cells from renal tubular antigen (Fx1A)-immunized rats and activated these cells in vitro to express the MHC Class lb molecule Qa-1. Vaccination of Lewis rats with 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-gamma 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 in Qa-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.

Original languageEnglish
Pages (from-to)1058-1067
Number of pages10
JournalJournal of the American Society of Nephrology
Volume23
Issue number6
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

Keywords

  • ACTIVE HEYMANN NEPHRITIS
  • RENAL TUBULAR ANTIGEN
  • MULTIPLE-SCLEROSIS
  • MEMBRANOUS NEPHROPATHY
  • HELPER-CELLS
  • IDENTIFICATION
  • INHIBITION
  • DEPLETION
  • RECEPTOR
  • RATS

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