JNK1 is essential for CD8+ T cell-mediated tumor immune surveillance
JNK1 is essential for CD8+ T cell-mediated tumor immune surveillance
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DOI：
10.4049/jimmunol.175.9.5783
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发表时间：
2005-11-01
影响因子：
4.4
通讯作者：
Yin, ZN
中科院分区：
文献类型：
--
作者：
Gao, YF;Tao, J;Yin, ZN
JNK 1在调节CD 4（+）和CD 8（+）T细胞的效应功能中具有不同的作用。然而，JNK 1在肿瘤免疫监视中的功能尚不清楚。在这项研究中，我们表明，类似于IFN-γ（-/-）小鼠，JNK 1（-/-）小鼠是高度敏感的黑色素瘤细胞系B16和淋巴瘤细胞系EL-4接种后的肿瘤发展。使用T细胞去除和重建方法，我们表明来自JNK 1（-/-）小鼠的CD 8（+）T细胞，而不是CD 4（+）T细胞，是肿瘤易感性的原因。JNK 1（-/-）CD 8（+）T细胞在体外被抗CD 3/抗CD 28抗体或负载特异性Ag的树突状细胞激活后，在早期IFN-γ基因转录和产生方面具有内在缺陷。JNK 1（-/-）CD 8（+）T细胞中IFN-γ产生受损与T-bet和Eomesodermin表达减少相关，表明JNK 1调节CD 8（+）T细胞的转录程序。最后，JNK 1（-/-）CD 8（+）T细胞显示穿孔素表达减少和CTL功能受损。综上所述，我们的研究结果表明，JNK 1通过调节CD 8（+）T细胞的效应功能在肿瘤免疫监视中发挥重要作用。
JNK1 has divergent roles in regulating the effector functions of CD4(+) and CD8(+) T cells. However, the function of JNK1 in tumor immune surveillance is unknown. In this study, we show that similar to IFN-gamma(-/-) mice, JNK1(-/-) mice are highly susceptible to tumor development after inoculation of both melanoma cell line B16 and lymphoma cell line EL-4. Using T cell depletion and reconstitution approaches, we show that CD8(+) T cells, but not CD4(+) T cells, from JNK1(-/-) mice are responsible for tumor susceptibility. JNK1(-/-) CD8(+) T cells have an intrinsic defect in early IFN-gamma gene transcription and production after activation by either anti-CD3/anti-CD28 Abs or dendritic cells loaded with specific Ag in vitro. The impaired IFN-gamma production in JNK1(-/-) CD8(+) T cells is associated with reduced expression of both T-bet and Eomesodermin, indicating that JNK1 regulates the transcription program of CD8(+) T cells. Finally, JNK1(-/-) CD8(+) T cells showed reduced perforin expression and impaired CTL function. Taken together, our results demonstrate that JNK1 plays an important role in tumor immune surveillance through regulating the effector functions of CD8(+) T cells.