Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4⁺CD25^–LAP⁺ T cells

Nature Medicine 12: 627 - 635 (2006)¹

Speaker: 鄭自勝                                   Time: 15:10-16:00, Sep. 27, 2006

Commentator: 徐麗君 老師               Place: Room 601

Abstract:

    Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). MS, which is a T_H1-type autoimmune response against myelin, results in nervous system inflammation. Intravenous administration of CD3-specific antibody has shown efficacy in animal models of autoimmune diseases, but the side effects limit its chronic use². Previously, the authors have found that mucosal administration of autoantigens would induce regulatory T cells with surface latency-associated peptide (LAP). These T cells are preferentially induced at mucosal surfaces and secrete transforming growth factor β (TGF-β)³. The authors hypothesized that orally administered CD3-specific antibody would bind to T cells in the gut and induce regulatory T cells without potential side effects. First, the author investigated the effects of anti-CD3 antibody administrationorally and intravenously. They found the mice appeared ill after intravenous CD3-specific antibody but not after oral administration. Next, the author investigated the dose effects on LAP⁺ T cells induction and enhancement of LAP⁺ T cell regulatory function when anti-CD3 antibody administrated to mice orally. Finally, the author isolated mesenteric T cells from mice fed CD3 antibody and intravenously transferred to naïve mice with or without anti-TGF-β antibody treatment, and found these T cells induce immune tolerance through a TGF-β dependent mechanism. Therefore, oral administration of CD3-specific antibody may be clinically applicable for the treatment of human autoimmune conditions.

References:

1. Ochi, H. et al. Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4⁺ CD25^- LAP⁺ T cells. Nat Med. 12, 617-618 (2006).

2. Chatenoud, L. CD3-specific antibody-induced active tolerance: from bench to bedside. Nat. Rev. Immunol. 3, 123–132 (2003).

3. Zhang, X. et al. Activation of CD25⁺ CD4⁺ regulatory T cells by oral antigen administration. J. Immunol. 167, 4245–4253 (2001).