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.
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Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA. davidlo@scripps.edu
D000818:Animals; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology*