Role of costimulatory molecules in autoimmunity.

The precise mechanisms by which self-reactive T cells are activated and tolerance to self-antigens is broken are still not fully understood. It is widely accepted that dysregulation of costimulation contributes to the initiation and maintenance of autoimmunity due to activation of self-reactive T cells. Many of the costimulatory molecules thought to be essential for T cell activation have been identified. The CD28/CD152 (CTLA-4)-CD80/CD86 and CD40-CD154 (CD40 ligand) interactions are such receptor/ligand pairs that have been shown to be important in interactions between antigen-presenting cells and T cells. In vivo studies using costimulatory molecule-specific antibodies and fusion proteins and genetically manipulated animals have greatly increased our understanding of the role of these costimulatory molecules in the regulation of cellular processes that lead to autoimmunity and resultant autoimmune diseases.