T-cell biology, tolerance, and regulation

Abstract The critical role of T lymphocytes (T cells) in the pathogenesis of systemic lupus erythematosus (SLE) has long been recognized. Direct evidence of the role of T cells in SLE includes the finding that depletion of T cells in lupus-prone mice blocks disease development (Wofsy and Seaman, 1987) and that athymic mice do not develop SLE (Mihara et al., 1988). The key role of T cells in the pathogenesis of SLE has been attributed to the broad immune activities of these cells, which include but are not limited to the provision of help to B cells for the production of (auto)antibodies and the release of many cytokines that can modulate the differentiation, number, and function of other immune cells. Since multiple T-cell functional activities appear to be altered or display abnormalities in SLE, it follows that aberrations of cell activation and responsiveness to antigenic stimulation can have deleterious consequences, particularly when involving self-reactive T cells. Hyperactive T cells in SLE also infiltrate organs and contribute to tissue inflammation and damage because of their dysregulated control, abnormal cell interactions, and local production of proinflammatory cytokines.