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CD8+ regulatory T cells induced by T cell vaccination protect against autoimmune nephritis.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2012 Jun; Vol. 23 (6), pp. 1058-67. Date of Electronic Publication: 2012 Apr 05. - Publication Year :
- 2012
-
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 Ib 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-γ 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.
- Subjects :
- Analysis of Variance
Animals
Autoantibodies immunology
Autoantibodies metabolism
Autoimmune Diseases metabolism
Autoimmune Diseases pathology
CD4-Positive T-Lymphocytes metabolism
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Glomerulonephritis, Membranous metabolism
Glomerulonephritis, Membranous pathology
Humans
Immunohistochemistry
Male
Rats
Rats, Inbred Lew
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction methods
Receptors, Antigen, T-Cell, alpha-beta biosynthesis
Sampling Studies
T-Lymphocytes immunology
Autoimmune Diseases immunology
CD8-Positive T-Lymphocytes metabolism
Cytokines metabolism
Glomerulonephritis, Membranous immunology
Receptors, Antigen, T-Cell, alpha-beta immunology
Vaccination methods
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 23
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 22491420
- Full Text :
- https://doi.org/10.1681/ASN.2011090914