L2   THE ROLE OF T AND DENDRITIC CELLS IN AUTOIMMUNITY

Zöller M., Dept. of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg, Germany.

In organ-specific as well as systemic autoimmune diseases. immunological, genetic and/or environmental factors may play critical roles in the induction of pathology. From the immunological point of view both autoantibodies and self-reactive T cells can be involved. While much is known on the cellular basis for autoantibody formation, especially the participation of helper T lymphocytes is poorly defined. There is consense on a disbalance between the T helper 1 (TH) and the TH2 subtypes which can be self-perpetuing, since both TH subtypes are mutually counterregulated. Consequently, application of IL-10 has been shown to be of therapeutic benefit in some autoimmune diseases. In which way are dendritic cells being involved? Initiation of a T cell response essentially requires an antigenic peptide presented by MHC molecules and a second signal provided by costimulatory molecules. Contact of the TCR with a nominal antigen in the absence of a costimulatory signal leads to T cell anergy and is one of the safeguard mechanisms of the peripheral tolerance. There are several pairs of costimulatory molecules and their ligands expressed by antigen presenting cells and T cells, respectively, one of the best known pairs being CD80 / CD86 and CD28 / CTLA. Occupying CD80 / CD86 by soluble CTLA-4 has been successfully used in the treatment of autoimmune disease. Last but not least, apoptosis is an important feature in keeping a balanced immune system. In fact, mice with a defect in FAS or FAS ligand suffer from an autoimmune and lymphoproliferative syndrome. The complexity of the disturbed interplay between T cell activation, regulatory cytokines, costimulatory molecules and induction of apoptosis will be demonstrated in a model of chronic inflammatory bowel disease, which can be prevented by the blockade or absence of CD44v7, one of the costimulatory molecules on antigen presenting cells.