T Cell Repertoire in Lupus: Autoreactive T Cells in Central and Peripheral Selection

Abstract

Systemic lupus erythematosus (SLE) is an immune disorder characterized by the presence of T and B cells which drive a pathogenic autoimmune response. Autoreactive T effector cells naturally arise during the process of development in the thymus, but most are removed by several self-tolerance mechanisms. Self-antigen recognizing T cells emigrating from the thymus are normally prevented from causing cellular or tissue damage by peripheral tolerance mechanisms. While we understand much about how self-antigens are presented to T cells and the mechanisms to remove those T cells or convert them into regulatory T cells in thymus and peripheral lymphoid organs, we understand much less about the derivation of potentially pathogenic self-reactive T cells in autoimmune disease. It is not clear whether individuals with autoreactive T cell activation have an altered T cell receptor repertoire of naïve T cells that have matured to immunocompetence as effector cells or whether the pathogenic process involves altered activation of immunocompetent T cells in the periphery. There is increasing evidence that the autoantibodies that characterize SLE result from an interaction of B cells with self-reactive T cells. Here we summarize the evidence for autoreactive T cells in both lupus mouse models and in patients with SLE and discuss the evidence for either altered T cell selection or altered T cell activation in SLE, which has implications for both pathogenesis and treatment