A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5
A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5
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DOI：
10.4049/jimmunol.167.12.6877
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发表时间：
2001-12-15
影响因子：
4.4
通讯作者：
Hamaoka, T
中科院分区：
文献类型：
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作者：
Iwasaki, M;Mukai, T;Hamaoka, T
最近发现IL-12可诱导TCR触发的小鼠T细胞产生CCR5。考虑到STAT4是最关键的IL-12信号分子，本研究探讨了STAT4在诱导CCR5表达中的作用。用抗CD3+抗CD28单抗刺激野生型(WT)和STAT4缺陷(-/-)小鼠的T细胞可诱导IL-12R，但干扰素-γ(-/-)缺陷T细胞的IL-12R水平低于野生型(WT)。IL-12诱导TCR触发的WT T细胞表达CCR5。相反，TCR触发的STAT4(-/-)T细胞未能表达CCR5以响应IL-12。IL-12刺激可诱导可检测到的CCR5在干扰素-γ(-/-)T细胞上的表达。在干扰素-γ(-/-)T细胞培养中加入重组干扰素-γ，特别是在TCR触发过程中，可恢复CCR5的表达。然而，补充重组干扰素-γ不能诱导STAT4(-/-)T细胞表达CCR5。这些结果表明，对于CCR5在T细胞上的诱导，1)STAT4起着不可或缺的作用；2)这种作用不是简单地补充干扰素-γ所能替代的；3)干扰素-γ依赖于STAT4的存在而增强CCR5的诱导。
IL-12 was recently shown to induce CCR5 on TCR-triggered mouse T cells. Considering that STAT4 is the most critical of IL-12 signaling molecules, this study investigated the role for STAT4 in the induction of CCR5 expression. IL-12R was induced by stimulation with anti-CD3 plus anti-CD28 mAb similarly on T cells from wild-type (WT) and STAT4-deficient (STAT4(-/-)) mice, but the levels of IL-12R induced on IFN-gamma -deficient (IFN-gamma (-/-)) T cells were lower compared with WT T cells. Exposure of TCR-triggered WT T cells to IL-12 induced CCR5 expression. In contrast, TCR-triggered STAT4(-/-) T cells failed to express CCR5 in response to IL-12. IL-12 stimulation induced detectable albeit reduced levels of CCR5 expression on IFN-gamma (-/-) T cells. Addition of rIFN-gamma to cultures of IFN-gamma (-/-) T cells, particularly to cultures during TCR triggering resulted in restoration of CCR5 expression. However, CCR5 expression was not induced in STAT4(-/-) T cells by supplementation of rIFN-gamma. These results indicate that for the induction of CCR5 on T cells, 1) STAT4 plays an indispensable role; 2) such a role is not substituted by simply supplementing IFN-gamma; and 3) IFN-gamma amplifies CCR5 induction depending on the presence of STAT4.