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Inhibiting TNF-alpha activity prevents tissue destruction without inhibiting retinal T cell infiltration in experimental autoimmune uveoretinitis (EAU) in Lewis rats. To further determine the role of TNF-alpha in autoimmune uveitis we characterized T cells isolated from retinae after treatment with a TNF-alpha antagonist. TNF-alpha activity was neutralized in vivo with a p55 TNF-alpha receptor-Ig fusion protein (sTNFr-Ig), administered 8 and 10 days after induction of EAU with heterologous retinal antigens. Retinal T-cell phenotype expression was examined by flow cytometry with respect to OX22 status (CD45RBlow or CD45RBhigh), activation (OX40 and CD25 expression) and rate of T-cell apoptosis (Annexin V+PI- expression). Lymphocyte reactivity was assessed by proliferation responses and cytokine production to retinal antigens. Despite greater than 40% of CD4+ T cells being activated at the height of disease, the proportion of OX22low expression was reduced and T cells exhibited reduced IFN-gamma and elevated IL-4 production. Retinal T cells maintained antigen-specific proliferation and demonstrated a low apoptotic rate. Although in both animal groups, comparable numbers of T cells were isolated, neutralizing TNF activity suppressed Th1 effector mechanisms protecting against target organ damage.

Original publication

DOI

10.1006/jaut.1998.0197

Type

Journal article

Journal

J Autoimmun

Publication Date

06/1998

Volume

11

Pages

255 - 264

Keywords

Animals, Anterior Chamber, Autoimmune Diseases, Biomarkers, Cell Division, Cell Movement, Female, Immunoconjugates, Immunoglobulin G, Interferon-gamma, Interleukin-4, Neutralization Tests, Phenotype, Rats, Rats, Inbred Lew, Receptors, Tumor Necrosis Factor, Retinitis, T-Lymphocyte Subsets, Tumor Necrosis Factor-alpha, Uveitis