Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Immunol. 2010 Sep 15;185(6):3401-7. doi: 10.4049/jimmunol.1000836. Epub 2010 Aug 18.
Mucosal (nasal or oral) administration of anti-CD3 mAb is effective in ameliorating animal models of autoimmunity (experimental autoimmune encephalomyelitis, diabetes, and lupus) by inducing LAP(+) regulatory T cells. We tested this approach in an arthritis model using type II collagen. We found that nasal anti-CD3 was more effective than oral anti-CD3 in attenuating the development of arthritis. Nasal anti-CD3 induced a LAP(+) regulatory T cell that secreted high levels of IL-10 and suppressed collagen-specific T cell proliferation and anti-collagen Ab production. However, neither nasal nor oral anti-CD3 attenuated disease when given to animals with ongoing arthritis, and this was associated with a lack of induction of LAP(+) regulatory T cells. We found, however, that coadministration of a novel emulsome adjuvant, which enhances Th2 responses, resulted in the induction of LAP(+) regulatory T cells and suppression of ongoing arthritis by both nasal and oral anti-CD3. Suppression of arthritis by mucosal anti-CD3 was associated with less joint damage, a decrease of TNF-alpha and IFN-gamma mRNA expression in joints, and a reduction in anti-collagen Abs. These results demonstrate that mucosal anti-CD3 therapy may serve as a therapeutic approach in arthritis and that the biologic effect is enhanced by an emulsome-based adjuvant.
黏膜（鼻内或口服）给予抗 CD3 mAb 通过诱导 LAP(+)调节性 T 细胞，在改善自身免疫动物模型（实验性自身免疫性脑脊髓炎、糖尿病和狼疮）方面是有效的。我们使用 II 型胶原在关节炎模型中测试了这种方法。我们发现鼻内抗 CD3 比口服抗 CD3 更能减轻关节炎的发展。鼻内抗 CD3 诱导产生了分泌高水平 IL-10 的 LAP(+)调节性 T 细胞，抑制胶原特异性 T 细胞增殖和抗胶原 Ab 的产生。然而，当给予患有持续性关节炎的动物时，鼻内或口服抗 CD3 均不能减轻疾病，这与缺乏诱导 LAP(+)调节性 T 细胞有关。然而，我们发现，给予一种新型乳剂佐剂（增强 Th2 反应）可诱导 LAP(+)调节性 T 细胞，并抑制鼻内和口服抗 CD3 对持续性关节炎的作用。黏膜抗 CD3 抑制关节炎与关节损伤减少、关节中 TNF-α和 IFN-γmRNA 表达减少以及抗胶原 Ab 减少有关。这些结果表明，黏膜抗 CD3 治疗可能是关节炎的一种治疗方法，乳剂佐剂增强了其生物学效应。
