Regulation of ocular inflammation - what experimental and human studies have taught us

Study of models of ocular autoimmunity and of autoimmune uveitis in humans has lead to a shift in the perceived nature of immune privilege from one ba sed on anatomical isolation oft lie eye to a more dynamic, active process o f immune tolerance. Using a variety of available models, the basis for this dynamic process of immune regulation is reviewed. The protective role of h umoral immunity, the co-stimulatory function of B cells in EAU as well as t he influence of cytokines within the inflammatory cascade are outlined. Mod ulation of the immune response and in particular the possible role of macro phages is explored. Within the current paradyme, a major effector cell is t he CD4+ lymphocyte. Its maturation into a Th1 or Th2 phenotype process appe ars dependent on a number of exogenous factors, which while genetically det ermined can be manipulated prior to disease onset, Activation of CD4+ cells is dependent on presentation of immunoreactive peptide fragments, These fr agments are well characterized in the Lewis rat for S-Ag and interphotorece ptor retinoid binding protein (IRBP). Mapping of the immunoreactivity to S- Ag has been recently completed in uveitis patients. An overlap with certain determinants identified in experimental models has been observed, in at le ast 2 disease entities. However, the response profile is not Fixed in time and is subject to determinant spread. Future studies will be aimed at ident ifying with more detail immunologic triggers of inflammation in patients. a nd at better defining the interplay between effector and regulatory pathway s both in the eye and in the systemic circulation. Published by Elsevier Sc ience Ltd.