A role for CD8+ T cells in an autoantibody response (44.7)

Abstract

IL-2-deficient mice develop a spontaneous systemic autoimmune disease and on the BALB/c background die at 3-4 weeks due to hypoxia from autoimmune hemolytic anemia (AIHA). These mice develop progressive lymphadenopathy due to the accumulation of CD4+ and CD8+ T cells. It is known that CD4+ T cells are necessary for disease progression and we have previously shown that IL-2-KO CD4+ T cells from sick mice can transfer AIHA and lymphadenopathy to recipient mice. As CD8+ T cells also accumulate during disease, we asked whether these cells play a role in the development of autoimmune disease. To address this, we depleted CD8+ T cells by treating mice twice a week with anti-CD8α (clone 2.43). Elimination of CD8+ T cells for two weeks resulted in an augmentation of survival from 3-4 weeks to 3 months. The number and activation state of the CD4+ T cells and B cells was decreased, and the development of red blood cell (RBC)-specific antibodies delayed. Our results suggest that autoreactive CD8+ T cells contribute to the initiation and/or propagation of lymphoproliferation and pathogenesis of autoimmunity. Both CD4+ and CD8+ T cells from the IL-2-deficient mice produce IFNγ in response to RBC antigens. We are currently addressing the importance of these autoreactive CD8+ T cells relative to that of the self-reactive CD4+ T cells. We are also evaluating the possible mechanisms by which CD8+ T cells influence the disease process.