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 based on anatomical isolation of the eye to a more dynamic, active process of immune tolerance. Using a variety of available models, the basis for this dynamic process of immune regulation is reviewed. The protective role of humoral immunity, the co-stimulatory function of B cells in EAU as well as the influence of cytokines within the inflammatory cascade are outlined. Modulation of the immune response and in particular the possible role of macrophages is explored. Within the current paradyme, a major effector cell is the CD4+ lymphocyte. Its maturation into a Th1 or Th2 phenotype process appears dependent on a number of exogenous factors, which while genetically determined can be manipulated prior to disease onset. Activation of CD4+ cells is dependent on presentation of immunoreactive peptide fragments. These fragments are well characterized in the Lewis rat for S-Ag and interphotoreceptor 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 least 2 disease entities. However, the response profile is not fixed in time and is subject to determinant spread. Future studies will be aimed at identifying with more detail immunologic triggers of inflammation in patients, and at better defining the interplay between effector and regulatory pathways both in the eye and in the systemic circulation.
de Smet
M D
MD
Department of Ophthalmology, University of Amsterdam, the Netherlands. m.d.desmet@amc.uva.nl
Chan
C C
CC
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D019393:Arrestin / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D005136:Eye Proteins; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D012177:Retinol-Binding Proteins / Q000276:immunology; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
D019393:Arrestin; D016207:Cytokines; D005136:Eye Proteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial