Oral tolerance: immune mechanisms and the generation of Th3-type TGF-beta-secreting regulatory cells
Oral tolerance: immune mechanisms and the generation of Th3-type TGF-beta-secreting regulatory cells
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DOI：
10.1016/s1286-4579(01)01456-3
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发表时间：
2001-09-01
影响因子：
5.8
通讯作者：
Weiner, HL
中科院分区：
文献类型：
--
作者：
Weiner, HL
口服免疫耐受是目前公认的诱导外周免疫耐受的方法。口服耐受性已成功用于治疗自身免疫性疾病的动物模型，并正在人类疾病中进行测试。低剂量的口服抗原诱导主动抑制，而高剂量诱导克隆无能和删除。口服抗原优先产生Th 2（IL-4/IL-10）-或Th 3（TGF-β）-型应答。Th 3型细胞是一种独特的T细胞亚群，主要分泌TGF-β，为伊加提供帮助，并对Th 1和其他免疫细胞具有抑制特性。Th 3型细胞似乎与Th 2细胞不同，因为在肠道中具有抑制特性的CD 4（+）TGF-β分泌细胞已从IL-4缺陷动物产生。通过与TGF-β、IL-4、IL-10和抗IL-12一起培养，可以增强来自TCR转基因小鼠的Th 0前体的Th 3型细胞的体外分化。因为由口服抗原产生的调节性T细胞以抗原特异性方式被触发，但以抗原非特异性方式被抑制，所以当它们在靶器官处遇到喂食的自身抗原时，它们介导“旁观者抑制”。因此，粘膜耐受可用于治疗本质上不是自身免疫性的炎症过程。粘蛋白抗原也被用于治疗中风和阿尔茨海默病的动物模型。低剂量口服耐受的诱导通过口服施用IL-4和IL-10而增强。将抗原偶联至CTB或施用Flt-3配体增强口服耐受性。抗B7.2而非抗B7.1阻断低剂量而非高剂量口服耐受。高剂量口服耐受性被抗CTLA-4阻断。CD 25（+）CD 4（+）调节性T细胞功能似乎也与TFG-β相关。(C)2001版，科学与医学，Elsevier SAS。
Oral tolerance is a tong recognized method to induce peripheral immune tolerance. Oral tolerance has been used successfully to treat animal models of autoimmune diseases and is being tested in human diseases. Low doses of oral antigen induce active suppression, whereas high doses induce clonal anergy and deletion. Oral antigen preferentially generates a Th2(IL-4/IL-10)- or a Th3(TGF-beta)-type response. Th3-type cells are a unique T-cell subset which primarily secrete TGF-beta, provide help for IgA and have suppressive properties for Th1 and other immune cells. Th3-type cells appear distinct from the Th2 cells as CD4(+) TGF-beta -secreting cells with suppressive properties in the gut have been generated from IL-4-deficient animals. In vitro differentiation of Th3-type cells from Th0 precursors from TCR transgenic mice is enhanced by culture with TGF-beta, IL-4, IL-10 and anti-IL-12. Because regulatory T cells generated by oral antigen are triggered in an antigen-specific fashion but suppress in an antigen-nonspecific fashion, they mediate 'bystander suppression' when they encounter the fed autoantigen at the target organ. Thus, mucosal tolerance can be used to treat inflammatory processes that are not autoimmune in nature. Mucosal antigen has also been used to treat animal models of stroke and of Alzheimer's disease. Induction of low-dose oral tolerance is enhanced by oral administration of IL-4 and IL-10. Coupling antigen to CTB or administration of Flt-3 ligand enhances oral tolerance. Anti-B7.2 but not anti-B7.1 blocks low-dose, but not high-dose oral tolerance. High-dose oral tolerance is blocked by anti-CTLA-4. CD25(+) CD4(+) regulatory T-cell function also appears to be related to TFG-beta. (C) 2001 Edition scientifiques et medicales Elsevier SAS.