Wynn T A, Jankovic D, Hieny S, Zioncheck K, Jardieu P, Cheever A W, Sher A
Host-Parasite Relations Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 1995 Apr 15;154(8):3999-4009.
To assess the role of IFN-gamma in the in vivo regulation of Th subset differentiation by IL-12, schistosome egg-induced Th2 responses and granuloma formation were studied in IFN-gamma knock-out (gamma KO) mice in which the absence of endogenous IFN-gamma is assured. Rather than suppressing pathology and eosinophilia as observed in wild-type animals, exogenous IL-12 in egg-injected gamma KO mice exacerbated Th2-dependent granuloma formation while failing to reduce peak tissue eosinophilia. Similarly, instead of inhibiting its production, IL-12 caused a dramatic increase in serum IgE levels in gamma KO animals after egg injection. Although the suppressive effects of IL-12 on Th2 responses were blocked in the absence of IFN-gamma, lymphocyte proliferation and IL-2 production were enhanced, a phenomenon which may underlie the observed exacerbation of egg-induced pathology. These findings formally establish that IL-12 inhibits Th2 development indirectly in vivo through the stimulation of IFN-gamma synthesis. In contrast, its promotion of Th1-associated responses seems to be at least partly a result of the direct action of the cytokine.
为评估γ干扰素在白细胞介素-12对Th亚群分化的体内调节中的作用，我们在确保内源性γ干扰素缺失的γ干扰素基因敲除（γKO）小鼠中研究了血吸虫卵诱导的Th2反应和肉芽肿形成。与在野生型动物中观察到的抑制病理和嗜酸性粒细胞增多不同，注射虫卵的γKO小鼠体内的外源性白细胞介素-12加剧了Th2依赖性肉芽肿形成，同时未能降低组织嗜酸性粒细胞增多的峰值。同样，白细胞介素-12在注射虫卵后的γKO动物中并未抑制血清IgE水平的产生，反而使其显著升高。尽管在缺乏γ干扰素的情况下，白细胞介素-12对Th2反应的抑制作用被阻断，但淋巴细胞增殖和白细胞介素-2的产生却增强了，这一现象可能是观察到的虫卵诱导病理加剧的基础。这些发现正式证实，白细胞介素-12在体内通过刺激γ干扰素的合成间接抑制Th2的发育。相比之下，它对Th1相关反应的促进作用似乎至少部分是细胞因子直接作用的结果。
