The relationship of inflammation and initiation of autoimmune disease: role of TNF super family members.

Abstract

In normal people, autoreactive T cells can be deleted, either in the thymus or in the periphery, following presentation of self-peptides by host antigenpresenting cells (APCs) to self-reactive T cells (Kurts et al. 1996, 1998a,b). Breakdown in this putative tolerance mechanism is believed to contribute to autoimmunity in genetically susceptible individuals. Type I diabetes mellitus is characterized by infiltration of the islets of Langerhans by immune cells, which ultimately destroy the insulin-producing β-cells by T cellmediated mechanisms. The T cell-mediated nature of this autoimmunity requires that APCs not only have to present islet antigen released from β-cells but also have to deliver signals that promote survival of the self-reactive T cells. Identification of the cells and events that initiate and maintain this anti-islet inflammatory response is vital in the development of therapeutic strategies towards diabetes.