A mechanism underlying synergy between IL-12 and IFN-gamma-inducing factor in enhanced production of IFN-gamma.
A mechanism underlying synergy between IL-12 and IFN-gamma-inducing factor in enhanced production of IFN-gamma.
复制标题
IL-12 和 IFN-γ 诱导因子之间协同作用增强 IFN-γ 产生的潜在机制。
DOI：
--
复制
发表时间：
1997
影响因子：
4.4
通讯作者：
Hiromi Fujiwara
中科院分区：
文献类型：
--
作者：
Hyun;S. Maruo;M. Tomura;Jie Mu;T. Hamaoka;K. Nakanishi;Steven C. Clark;M. Kurimoto;H. Okamura;Hiromi Fujiwara
IL-12和IFN-γ诱导因子（IGIF）具有刺激T细胞产生IFN-γ的能力。使用IL-12响应性T细胞克隆2D 6，我们研究了这两种细胞因子如何协同产生IFN-γ。从含有rIL-12的培养物获得的2D 6响应于rIGF产生IFN-γ。在单独用rIL-12或rIGF刺激后，来自剥夺IL-12 24小时的培养物的2D 6仅产生边缘水平的IFN-γ产生。然而，用两种细胞因子同时刺激这些2D 6细胞导致IFN-γ产生水平显著提高。2D 6也可以在rIL-2而不是rIL-12的存在下维持。用rIL-12（2D 6（IL-12））或rIL-2（2D 6（IL-2））维持的2D 6细胞系表现出不同的IGIF反应性：两种细胞系对rIL-2或rIL-12的反应相似，而2D 6（IL-12）或2D 6（IL-2）分别表现出高或边缘的IGIF反应性。2D 6（IL-12）细胞系表达IGIF受体（IGIFR），而2D 6（IL-2）细胞系不表达IGIF受体。2D 6（IL-12）过夜暴露于rIL-2降低IGIFR表达，相反，2D 6（IL-2）暴露于rIL-12恢复IGIFR表达。这些2D 6系的IGIFR表达与响应rIGIF产生IFN-γ的能力相关。还发现用抗CD 3加抗CD 28 mAb刺激并随后用rIL-12培养的纯化的初始T细胞表达IGIFR并在IGIF刺激后诱导增强的IFN-γ产生。这些结果表明IL-12诱导IGIFR代表了IL-12和IGIF在IFN-γ产生中协同作用的机制之一。
IL-12 and IFN-gamma-inducing factor (IGIF) have the capacity to stimulate IFN-gamma production by T cells. Using an IL-12-responsive T cell clone, 2D6, we investigated how these two cytokines collaborate for IFN-gamma production. 2D6 obtained from cultures containing rIL-12 produced IFN-gamma in response to rIGIF. 2D6 from cultures deprived of IL-12 for 24 h produced only marginal levels of IFN-gamma production following stimulation with either rIL-12 or rIGIF alone. However, simultaneous stimulation of these 2D6 cells with both cytokines resulted in strikingly enhanced levels of IFN-gamma production. 2D6 could also be maintained in the presence of rIL-2 instead of rIL-12. 2D6 lines maintained with rIL-12 (2D6(IL-12)) or rIL-2 (2D6(IL-2)) exhibited differential IGIF responsiveness: both lines responded similarly to rIL-2 or rIL-12, whereas the 2D6(IL-12) or 2D6(IL-2) exhibited high or marginal IGIF responsiveness, respectively. The 2D6(IL-12) line expressed IGIF receptor (IGIFR), whereas the 2D6(IL-2) did not. Overnight exposure of the 2D6(IL-12) to rIL-2 reduced IGIFR expression and conversely, exposure of the 2D6(IL-2) to rIL-12 restored IGIFR expression. IGIFR expression by these 2D6 lines correlated with the capacity to produce IFN-gamma in response to rIGIF. Purified naive T cells stimulated with anti-CD3 plus anti-CD28 mAb and subsequently cultured with rIL-12 were also found to express IGIFR and induce enhanced IFN-gamma production following IGIF stimulation. These results indicate that the induction of IGIFR by IL-12 represents one of the mechanisms underlying the synergy between IL-12 and IGIF in IFN-gamma production.