NEUTRALIZING TNF-ALPHA ACTIVITY MODULATES T-CELL PHENOTYPE AND FUNCTION IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS

Inhibiting TNF-alpha activity prevents tissue destruction without inhi biting retinal T cell infiltration in experimental autoimmune uveoreti nitis (EAU) in Lewis rats. To further determine the role of TNF-alpha in autoimmune uveitis we characterized T cells isolated from retinae a fter treatment with a TNF-alpha antagonist. TNF-alpha activity was neu tralized in vivo with a p55 TNF-alpha receptor-Ig fusion protein (sTNF r-Ig), administered 8 and 10 days after induction of EAU with heterolo gous retinal antigens. Retinal T-cell phenotype expression was examine d by flow cytometry with respect to OX22 status (CD45RB(low) or CD45RB (high)), activation (OX40 and CD25 expression) and rate of T-cell apop tosis (Annexin V+PI- expression). Lymphocyte reactivity was assessed b y proliferation responses and cytokine production to retinal antigens. Despite greater than 40% of CD4(+) T cells being activated at the hei ght of disease, the proportion of OX22(low) expression was reduced and T cells exhibited reduced IFN-gamma and elevated IL-4 production. Ret inal T cells maintained antigen-specific proliferation and demonstrate d a low apoptotic rate. Although in both animal groups, comparable num bers of T cells were isolated, neutralizing TNF activity suppressed Th 1 effector mechanisms protecting against target organ damage. (C) 1998 Academic Press.