Claessen A M, von Blomberg B M, De Groot J, Wolvers D A, Kraal G, Scheper R J
Department of Pathology, Free University Hospital, Amsterdam.
Immunology. 1996 Jul;88(3):363-7. doi: 10.1046/j.1365-2567.1996.d01-659.x.
Oral feeding of proteins causes peripheral T-cell tolerance, as revealed by reduced delayed-type hypersensitivity (DTH) reactivity after immunization. This type of tolerance can be due both to passive T-cell anergy and active immunosuppression. Using ovalbumin-fed mice we studied whether putatively immunostimulatory cytokines could break this state of mucosal tolerance. Cytokines were administered locally at the site of attempted sensitization. It was found that neither interleukin-2 (IL-2), interferon-gamma (IFN-gamma) nor granulocyte-macrophage colony-stimulating factor (GM-CSF) could restore the response to immunization. In contrast, local administration of IL-12 at the site of attempted immunization resulted in full recovery of DTH reactivity. The dichotomy between the two Th1 stimulatory cytokines IFN-gamma and IL-12 was also reflected by different effects on ovalbumin-specific antibody isotypes. Although both IFN-gamma and IL-12 downregulated serum IgG1-levels in tolerant mice, suggesting decreased ovalbumin-specific Th2 function, only local administration of IL-12 led to increased serum IgG2a levels. These results support the view that potentiation of Th1 effector function is critical for reversal of mucosal tolerance.
口服蛋白质会导致外周T细胞耐受，这在免疫后迟发型超敏反应（DTH）反应性降低中得到体现。这种耐受类型可能是由于被动T细胞无反应性和主动免疫抑制。我们使用喂食卵清蛋白的小鼠研究了假定的免疫刺激细胞因子是否能打破这种黏膜耐受状态。细胞因子在试图致敏的部位局部给药。结果发现，白细胞介素-2（IL-2）、干扰素-γ（IFN-γ）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）均不能恢复免疫反应。相反，在试图免疫的部位局部给予IL-12可使DTH反应性完全恢复。两种Th1刺激细胞因子IFN-γ和IL-12之间的差异也体现在对卵清蛋白特异性抗体亚型的不同影响上。虽然IFN-γ和IL-12均下调了耐受小鼠的血清IgG1水平，提示卵清蛋白特异性Th2功能降低，但只有局部给予IL-12会导致血清IgG2a水平升高。这些结果支持了这样一种观点，即增强Th1效应功能对于逆转黏膜耐受至关重要。
