RECOMBINANT ADENOVIRUS ENCODING GP100 MODULATES EXPERIMENTAL MELANIN-PROTEIN INDUCED UVEITIS (EMIU)

Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediat ed autoimmune uveitis induced by immunization with bovine uveal melani n protein. Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma antigen. A recombinant adenovirus construct encod ing gp100 (Ad2CMV-gp100) has been used as a vaccine for cancer therapy . This study examines the effect of Ad2CMV-gp100 on EMIU. To induce EM IU, rats were injected intraperitoneally on day 7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV-LacZ), or no virus. On day 21 after immunization, the right eye was processed fo r histology and the left eye was analysed for cytokines by quantitativ e reverse transcriptase-polymerase chain reaction. Western blot analys is showed that uveal melanin-protein contains gp100. In three independ ent experiments, ocular inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA was much lower in the rats which r eceived Ad2CMV-gp100 before immunization than in those that received A d2CMV-LacZ or no virus. No abnormalities developed in rats which recei ved Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100 injecti on prevents the development of EMIU, at least in part, through cytokin e regulation. (C) 1998 Academic Press Limited.