MacDonald T T, Monteleone G
Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton, UK SO16 6YD.
Trends Immunol. 2001 May;22(5):244-7. doi: 10.1016/s1471-4906(01)01892-0.
Oral tolerance is a well-characterized phenomenon in animals and is highly effective when induced as a treatment for experimental autoimmune disease. However, its use as a therapeutic modality for the treatment of autoimmune disease in humans has been disappointing. Much of the rationale for its use in humans is based on the finding that feeding antigen to rodents elicits regulatory T cells in Peyer's patches (PPs) that secrete immunosuppressive cytokines such as transforming growth factor (TGF)-beta. By contrast, human antigen-specific PP T-cell responses, and mucosal T-cell responses in general, are strongly biased towards T helper 1 (Th1) cells, which are pro-inflammatory rather than immunosuppressive. This is caused by the high local levels of interleukin (IL)-12 in PPs.
口服耐受是动物中一种特征明确的现象，作为实验性自身免疫性疾病的治疗方法诱导时非常有效。然而，其作为人类自身免疫性疾病治疗方式的应用却不尽人意。在人类中使用它的许多理论依据是基于这样的发现：给啮齿动物喂食抗体会在派尔集合淋巴结（PPs）中引发调节性T细胞，这些细胞会分泌免疫抑制细胞因子，如转化生长因子（TGF）-β。相比之下，人类抗原特异性PP T细胞反应以及一般的黏膜T细胞反应强烈偏向于促炎性而非免疫抑制性的辅助性T细胞1（Th1）。这是由PPs中白细胞介素（IL）-12的高局部水平所导致的。
