The Role Of Regulatory T Cells In Experimental Autoimmune Glomerulonephritis

Anti-glomerular basement membrane (anti-GBM) disease is characterized by antibodies and T cells directed against the Goodpasture antigen, the noncoilagenous domain of the alpha 3-chain of type IV collagen [alpha 3(IV)NC1] of the GBM. Consequences are the deposition of autoantibodies along the GBM and the development of crescentic glomerulonephritis (GN) with rapid loss of renal function. Forkhead box protein P3 (Foxp3) regulatory T (Treg) cells are crucial for the maintenance of peripheral tolerance to self-antigens and the prevention of immunopathology. Here. we use the mouse model of experimental autoimmune GN to characterize the role of Treg cells in anti-GBM disease. Immunization of DBA/1 mice with alpha 3(IV)NC1 induced the formation of alpha 3(IV)NC1specific T cells and antibodies and. after 8-10 wk, the development of crescentic GN. Immunization resulted in increased frequencies of peripheral Treg cells and renal accumulation of these cells in the stage of acute GN. Depletion of Treg cells during immunization led to enhanced generation of alpha 3(IV)NC1-specific antibodies and T cells and to aggravated GN. In contrast, depletion or expansion of the Treg cell population in mice with established autoimmunity had only minor consequences for renal inflammation and did not alter the severity of GN. In conclusion. our results indicate that in anti-GBM disease, Treg cells restrict the induction of autoimmunity against alpha 3(IV)NC1. However, Treg cells are inefficient in preventing crescentic GN after autoimmunity has been established.