Dysregulated CD8+ T cells promote antibody-mediated autoimmune disease (P4105)

Abstract

Abstract IFNγ-producing CD4+ and CD8+ T cells accumulate during systemic autoimmune disease in IL-2-deficient mice. CD4+ T cells are necessary for disease progression, and we have previously shown that IL-2-KO CD4+ T cells can transfer autoimmunity to recipient mice. However, the importance of CD8+ T cells to initiation and propagation of disease is unclear. Several groups have demonstrated a protective role for CD8+ T cells in inflammation and autoimmunity, while others have suggested a pathogenic role. To define the function of CD8+ T cells during spontaneous autoimmune disease, we depleted CD8+ T cells in IL-2-KO mice and evaluated the pathogenesis of autoimmunity. Elimination of CD8+ T cells for only two weeks resulted in a significant augmentation of survival, reduction in the number and activation state of the CD4+ T cells and B cells, and a delay in the development of erythrocyte (RBC)-specific antibodies. In untreated IL-2-KO mice, both CD4+ and CD8+ T cells produced IFNγ in response to RBC antigens. This upregulation indicates that autoreactive CD8+ T cells specific for RBC-antigens are present during disease. Our results suggest that autoreactive CD8+ T cells contribute to the initiation or propagation of lymphoproliferation and pathogenesis of autoimmunity. We are currently addressing the importance of these autoreactive CD8+ T cells relative to self-reactive CD4+ T cells. We are also evaluating the mechanisms by which CD8+ T cells promote the autoimmune disease process.