Anti-CD3 antibody ameliorates experimental autoimmune uveitis by inducing both IL-10 and TGF-β dependent regulatory T cells.
Chronic/recurrent autoimmune (idiopathic) uveitis is difficult to treat and they account for approximately 10% of legal blindness in the Western world. As it has been reported that anti-CD3 antibody can enhance T cell regulatory function, we investigated its effects in vivo on experimental autoimmune uveitis (EAU), a model for autoimmune uveitis in humans. B10RIII mice immunized with an uveitogenic peptide were treated with the F(ab')(2) fragment of anti-CD3 mAb either before or at clinical disease onset. Evaluation of EAU and cellular responses showed that disease was inhibited and the activation and expansion of pathogenic T cells selectively reduced, whereas functions of Treg in vivo were enhanced. Moreover, mice treated with anti-CD3 mAb were resistant to a second challenge with antigen and thus protected from recurrence of disease. Our results demonstrate that anti-CD3 mAb is a potent inhibitor of autoimmune uveitis.
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA.
Yan
Y
Ke
Guomin
G
Jiang
Deming
D
Sun
Henry J
HJ
Kaplan
Hui
H
Shao
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D017252:CD3 Complex / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*; D014605:Uveitis / Q000276:immunology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C556062:IL10 protein, mouse; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
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