Origin of late-onset autoimmune disease.

Autoimmune disease in the elderly is hypothesized to be caused by an imbalance in T-cell expansion and deletion after an encounter with self-antigens. A decrease in thymic output leads to a decreased pool of naive T cells in the periphery and to increased oligoclonal expansion of T cells. This expansion may be caused by stimulation with autoantigens that drive high-affinity interactions with self-antigens. Accumulation of presenescent, apoptosis-resistant, and proinflammatory T cells results in the growth of these autoreactive T cells. A decreased T-cell activation response that occurs with age leads to several defects that diminish the immune response.