c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 signaling pathways have divergent roles in CD8(+) T cell-mediated antiviral immunity.
c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 signaling pathways have divergent roles in CD8(+) T cell-mediated antiviral immunity.
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DOI：
10.1084/jem.20011481
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发表时间：
2002-04-01
影响因子：
15.3
通讯作者：
Oldstone, Michael B A
中科院分区：
文献类型：
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作者：
Arbour, Nathalie;Naniche, Denise;Homann, Dirk;Davis, Roger J;Flavell, Richard A;Oldstone, Michael B A
C-jun NH2末端激酶(JNK)在辅助性T细胞(Th)的增殖、分化和维持Th1/Th2极化中起重要作用。为了确定JNKs是否参与抗病毒T细胞免疫，以及JNK1和JNK2是否具有生物学差异，我们研究了JNK1和JNK2缺陷小鼠对淋巴细胞性脉络膜脑膜炎病毒(LCMV)的免疫应答。在LCMV感染后，野生型(JNK+/+)小鼠的脾CD8+T细胞增加了5-10倍。相比之下，感染JNK1CD8的−/−小鼠表现出明显较低的病毒特异性CD8+T细胞扩增。然而，JNK1−/−小鼠清除巨细胞病毒感染的动力学与JNK+/+小鼠相似。巨噬细胞病毒感染JNK1−/−动物的脾T细胞在病毒多肽刺激下产生干扰素γ。然而，在初始应答的高峰期，获得活化表型(CD44hi)的JNK1CD8+−/−T细胞比−/−+/+细胞更少，而更多的JNK1CD8+CD44hi细胞发生了凋亡。相比之下，感染巨细胞病毒的−/−小鼠比JNK+/+小鼠产生更多的病毒特异性CD8+T细胞。这些结果表明，在病毒感染过程中，JNK1和JNK2信号通路在T细胞反应中具有不同的作用。JNK1参与免疫应答过程中活化T细胞的存活，JNK2在体内控制CD8+T细胞的增殖。
c-Jun NH2-terminal kinases (JNK) play important roles in T helper cell (Th) proliferation, differentiation, and maintenance of Th1/Th2 polarization. To determine whether JNKs are involved in antiviral T cell immunity, and whether JNK1 and JNK2 bear biological differences, we investigated the immune responses of JNK1-deficient and JNK2-deficient mice to lymphocytic choriomeningitis virus (LCMV). After LCMV infection, wild-type (JNK+/+) mice had a 5- to 10-fold increase in splenic CD8+ T cells. In contrast, infected JNK1−/− mice showed a significantly lower virus-specific CD8+ T cell expansion. However, JNK1−/− mice cleared LCMV infection with similar kinetics as JNK+/+ mice. Splenic T cells from LCMV-infected JNK1−/− animals produced interferon γ after stimulation with viral peptides. However, fewer JNK1−/− T cells acquired an activated phenotype (CD44hi) and more JNK1−/−CD8+CD44hi cells underwent apoptosis than JNK+/+ cells at the peak of the primary response. In contrast, LCMV-infected JNK2−/− mice generated more virus-specific CD8+ T cells than JNK+/+ mice. These results indicate that JNK1 and JNK2 signal pathways have distinct roles in T cell responses during a viral infection. JNK1 is involved in survival of activated T cells during immune responses, and JNK2 plays a role in control of CD8+ T cell expansion in vivo.