T Cell Vaccination Protects against Active Heymann Nephritis: A CD8 T Cell Mechanism
Purpose: T cell vaccination (TCV) is a method to induce resistance to autoimmune diseases by priming the immune system with autoreactive T cells. Active Heymann nephritis (HN) is a rat autoimmune disease model of human membranous nephritis. The purpose of this study was to examine the effect of TCV on HN.
Methods: CD4 T cells from Fx1A immunised rats were isolated then activated with ConA, and then irradiated and used to immunise Lewis rats (TCV). HN was induced in Lewis rats with and without TCV by immunisation with (RAT/Fx1A). The molecular mechanisms of TCV were further investigated.
Results: TCV significantly protected against HN. Proteinuria was reduced at 10 and 12 weeks after immunisation with Fx1A in TCV rats, compared to control HN rats (p<0.05). There was significantly less glomerulosclerosis, tubular damage and interstitial infiltrates in the TCV group (p<0.01). Interstitial infiltrates of macrophages and CD8+ cells were also significantly decreased. In vitro cytotoxicity assays demonstrate a CD8 subset that kills Qa-1 expressing CD4 T cells.
Conclusion: TCV protects against HN. The effects of TCV may involve suppressive CD8 cells that recognize Qa-1 expressing CD4 cells.