Lee H O, Miller S D, Hurst S D, Tan L J, Cooper C J, Barrett T A
Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Medical School, Chicago, Illinois, USA.
Gastroenterology. 2000 Jul;119(1):129-38. doi: 10.1053/gast.2000.8542.
BACKGROUND & AIMS: Previous data suggest that oral antigen induces interferon (IFN)-gamma production in intestinal T cells. However, oral tolerance is associated with decreased production of IFN-gamma by T cells after antigen sensitization. The aim of this study was to examine the role of IFN-gamma in oral tolerance.
Oral tolerance was examined in BALB/c mice after the adoptive transfer of T cells from chicken ovalbumin (OVA(323-339))-specific, DO11.10 x RAG-1(-/-) T-cell receptor transgenic mice.
OVA feeding induced systemic tolerance of delayed-type hypersensitivity (DTH) and antibody responses. OVA feeding up-regulated IFN-gamma production by transgenic T cells in Peyer's patch and mesenteric lymph node but not splenic tissues. Treatment of OVA-fed mice with neutralizing monoclonal antibody to IFN-gamma prevented tolerance of DTH responses. Analysis of transgenic T-cell numbers in DTH sites by immunohistochemical staining suggested that induction of IFN-gamma by oral antigen decreased accumulation of transgenic T cells in cutaneous sites of antigen injection. IFN-gamma-deficient or wild-type DO11.10 and BALB/c mice were used to show that IFN-gamma production by donor transgenic T cells was critical for oral tolerance.
These data suggest that the induction of IFN-gamma by oral antigen contributes to systemic tolerance by decreasing migration of T cells to peripheral sites of inflammation.
先前的数据表明，口服抗原可诱导肠道T细胞产生干扰素（IFN）-γ。然而，口服耐受与抗原致敏后T细胞产生IFN-γ减少有关。本研究的目的是探讨IFN-γ在口服耐受中的作用。
在从鸡卵清蛋白（OVA(323-339)）特异性、DO11.10×RAG-1(-/-)T细胞受体转基因小鼠过继转移T细胞后，检测BALB/c小鼠的口服耐受情况。
喂食OVA可诱导迟发型超敏反应（DTH）和抗体反应的全身耐受。喂食OVA可上调派尔集合淋巴结和肠系膜淋巴结中转基因T细胞产生IFN-γ，但对脾组织无此作用。用抗IFN-γ中和单克隆抗体处理喂食OVA的小鼠可阻止DTH反应的耐受。通过免疫组织化学染色分析DTH部位的转基因T细胞数量表明，口服抗原诱导的IFN-γ减少了转基因T细胞在抗原注射皮肤部位的积聚。使用IFN-γ缺陷型或野生型DO11.10和BALB/c小鼠表明，供体转基因T细胞产生IFN-γ对口服耐受至关重要。
这些数据表明，口服抗原诱导IFN-γ通过减少T细胞向炎症外周部位的迁移而有助于全身耐受。
