Immune regulation: susceptibility and resistance to autoimmunity

Susceptibility and resistance to autoimmune diabetes appear to be regulated at several levels. Whereas the effector functions of autoimmunity are dependent on the antigen-specific responses of autoreactive T cells, the development of tissue-specific autoimmunity appears to be additionally dependent on tissue-specific factors. Thus, the recruitment of T lymphocytes into the vicinity of islet tissue is driven by the local production of chemokines with a pattern unique to islet tissue. The accumulation of lymphocytes triggers events that lead to the local development of new lymphoid tissue, enhancing the presentation of islet-specific antigens to the immune system. In the presence of additional genetic factors allowing persistent immune responses, autoreactivity is permitted to progress until end-stage autoimmune diabetes develops. My laboratory is studying the influence of tissue-specific factors and the genetic regulation of lymphocyte reactivity. An integrated understanding of these effects should lead to a more physiologic approach to prevention and treatment of autoimmune diabetes.