Neutralizing TNF-alpha activity modulates T-cell phenotype and function in experimental autoimmune uveoretinitis.

Journal article

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.

Authors: Dick, A; Duncan, L; Hale, G; Waldmann, H; Isaacs, J

• Publication status: Published
• Journal: Journal of autoimmunity
• Volume: 11
• Issue: 3
• Pages: 255-264
• Publication date: 1998-06-01
• DOI: 10.1006/jaut.1998.0197
• EISSN: 1095-9157
• ISSN: 0896-8411
• Language: English
• Keywords: Biological Markers; Retinitis; Interleukin-4; Interferon-gamma; Anterior Chamber; Cell Movement; Uveitis; Receptors, Tumor Necrosis Factor; Immunoglobulin G; Animals; Female; Immunoconjugates; Tumor Necrosis Factor-alpha; Rats, Inbred Lew; Rats; T-Lymphocyte Subsets; Autoimmune Diseases; Neutralization Tests; Cell Division; Phenotype