Drak2 is critical for the survival of autoreactive T cells

Drak2 is a serine/threonine kinase expressed in T cells and B cells. In the absence of Drak2 , mice are remarkably resistant to experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We tested if the absence of Drak2 affected other mouse models of autoimmune disease and found that Drak2−/− mice were completely resistant to type 1 diabetes when crossed to the NOD background. However, Drak2−/− mice were still susceptible to other models of autoimmunity including the T cell transfer model of colitis, collagen‐induced arthritis, and Systemic Lupus Erythematosus. In order to understand how Drak2 affects certain autoimmune diseases, we investigated the mechanism for the resistance to EAE and found that it is intrinsic to the T cells. There was a similar number of MOG‐specific T cells in the lymphoid organs of wildtype and Drak2−/− mice following immunization with MOG peptide. Surprisingly, Drak2−/− T cells entered the central nervous system, however the cells did not accumulate and cause damage like wildtype T cells. A higher proportion of the Drak2−/− T cells in the central nervous system were undergoing apoptosis compared to the wildtype T cells, which indicates that Drak2 is important for the survival of these autoreactive T cells. Moreover, in the NOD model, islet‐reactive T cells were more susceptible to death in the pancreatic draining lymph nodes in the absence of Drak2 . Together, these data suggest that Drak2 is important for the survival of activated T cells, and the absence of Drak2 inhibits autoimmune diseases in which the presence of the T cells in the target organ is required to perpetuate disease by decreasing the survival of the autoreactive T cells. This work is supported by the Juvenile Diabetes Research Foundation.