Experimental melanin-induced uveitis in the Fischer 344 rat is inhibited by anti-CD4 monoclonal antibody, but not by mannose-6-phosphate

Experimental melanin-induced uveitis (EMIU) is a rodent model of acute ante rior uveitis which was described in 1993. We investigated strain susceptibi lity, and age and gender characteristics of the model, undertook histologic al and immunohistochemical studies to investigate underlying cellular mecha nisms, and examined several treatment options. Rats were immunized with bov ine ocular melanin (250 mu g), and disease was followed by slit lamp examin ation. Lewis, Fischer 344 and Porton rats were found to be susceptible to E MIU, whereas Wistar-Furth, DA, and Hooded Wistar strains were resistant. EM IU was neither age- nor gender-dependent. In Fischer 344 rats, EMIU was cha racterized clinically by florid anterior segment inflammation. Histopatholo gical findings included infiltration of ciliary body and iris with mononucl ear cells and neutrophils. Both CD4(+) and CD8(+) T lymphocytes were promin ent. Rats were then treated with intraperitoneal injections of anti-CD4, an ti-CD8 or irrelevant isotype-matched MoAb on days -3, 0, 3, 6 and 9 with re spect to melanin immunization. Incidence of uveitis was significantly reduc ed in rats treated with a non-depleting cocktail of anti-CD4 MoAbs (P = 0.0 07), whereas a depleting anti-CD8 antibody had no effect on the disease. Ma nnose-6-phosphate inhibits lymphocyte migration in some models of T cell-me diated inflammation. This simple sugar was administered to additional rats via intraperitoneal osmotic pumps for 14 days following disease induction, but did not influence the uveitis. We conclude that EMIU is controlled by C D4(+) T cells, and disease may be abrogated by treatment with anti-CD4 MoAb s.