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

J Autoimmun. 1998 Jun;11(3):255-64. doi: 10.1006/jaut.1998.0197.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Chamber / pathology
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Biomarkers
  • Cell Division
  • Cell Movement
  • Female
  • Immunoconjugates / therapeutic use
  • Immunoglobulin G
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Neutralization Tests
  • Phenotype
  • Rats
  • Rats, Inbred Lew
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Retinitis / drug therapy
  • Retinitis / etiology
  • Retinitis / immunology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factor-alpha / immunology*
  • Uveitis / drug therapy
  • Uveitis / etiology
  • Uveitis / immunology*


  • Biomarkers
  • Immunoconjugates
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma