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

最後更新日期 : 2015-09-10

Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+CD25LAP+ 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 TH1-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 CD4CD25LAP+ 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 CD25CD4+ regulatory T cells by oral antigen administration. J. Immunol167, 4245–4253 (2001).

期刊名稱: Nature Medicine 12: 627-635, 2006
文章名稱: Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+CD25–LAP+ T cells
講者: 鄭自勝
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