The immune system uses powerful mechanisms to prevent and/or eliminate external and insurgent invaders inimical to well-being. Although the response is selective, "collateral damage" to healthy tissue can result from most defense mechanisms. A hallmark of the adaptive immune response is the selectivity of the response to antigens distinctive from self. This aversion to self reactivity (horror autotoxicus) , necessary for the well-being and survival of species bearing an adaptive immune system, is effected centrally during the development of the system and peripherally by antigen-directed and cell-mediated mechanisms that are specific to the antigen that incited the response. To some extent, these antigen-driven and cell-mediated peripheral mechanisms that regulate specifically the immune response serve as a back-up for the developmental selection mechanisms used to avoid reactions to self. Moreover, like any defense organization, the adaptive immune response must be highly regulated, particularly in susceptible sites like the eye and the brain.

The goal of this laboratory is to understand the mechanisms of the activation and function of antigen-specific regulatory T cells that develop during an immune response. Overall understanding the cell-mediated regulation of the immune response impacts immunization procedures and/or the management of autoimmune disorders. In collaboration with Dr. J. O'Rourke, the central model to investigate these regulatory T cells is focused on the "immune privilege" of the eye that activates antigen-specific regulatory T cells. Our studies include (1) The nature and function of ocular and circulating antigen presenting cells that activate regulatory T cells in the thymus and the spleen, (2), the mechanisms of the regulation of cell-mediated immunity to self and non-self antigens by antigen-specific thymic and in collaboration with Dr. A.Vella, splenic regulatory T cells, (3) the role of the sympathetic nervous system in the development of regulatory T cells. In collaboration with Dr. R. Clark a model for the regulation of autoimmune disease based on the ocular activation of regulatory T cells is under development