Scheper R J, von Blomberg M E, de Groot J, Wolvers D A, Kraal G, Claessen A M
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Ann N Y Acad Sci. 1996 Oct 31;795:403-9. doi: 10.1111/j.1749-6632.1996.tb52706.x.
Feeding of proteins causes peripheral T-cell tolerance, as revealed by reduced delayed-type hypersensitivity (DTH) reactivity after immunization. Using ovalbumin-fed mice, we studied whether putatively immunostimulatory cytokines could reverse this state of mucosal tolerance. It was found that local administration of neither IL-2, IFN-gamma, nor GM-CSF resulted in reversal of tolerance. In contrast, subcutaneous administration of IL-12 at the site of attempted immunization resulted in complete 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 Th1-related IgG2a levels. These results support the view that potentiation of Th1 effector function is critical for reversal of mucosal tolerance.
蛋白质喂养会导致外周T细胞耐受，这在免疫后迟发型超敏反应（DTH）反应性降低中得以体现。利用卵清蛋白喂养的小鼠，我们研究了假定具有免疫刺激作用的细胞因子是否能够逆转这种黏膜耐受状态。结果发现，局部给予白细胞介素-2（IL-2）、γ干扰素（IFN-γ）或粒细胞-巨噬细胞集落刺激因子（GM-CSF）均不能导致耐受的逆转。相反，在试图免疫的部位皮下注射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可导致血清Th1相关IgG2a水平升高。这些结果支持了以下观点，即增强Th1效应功能对于逆转黏膜耐受至关重要。
