King Susan B S, Knorn Anna M, Ohnmacht Caspar, Voehringer David
Institute for Immunology, University of Munich, Munich, Germany.
J Immunol. 2008 Jan 15;180(2):754-63. doi: 10.4049/jimmunol.180.2.754.
Th2 cells are important effector cells during allergic disorders and parasite infections. Efficient differentiation of Th2 cells requires signaling via the IL-4R and the transcription factor Stat6. Stat6 is further implicated in Th2 cell recruitment to the lung and might be required for the survival of memory Th2 cells. We analyzed the role of Stat6 in T cell expansion, survival, and recruitment to the lung using competitive adoptive transfer experiments and infection with the helminth parasite Nippostrongylus brasiliensis. Stat6 was not required in T cells or other cell types for recruitment of in vivo-generated Th2 cells to the lung. Functional analysis of Th2 memory cells revealed that Stat6 signaling in CD4 T cells was dispensable for memory cell generation, expansion, and cytokine secretion. However, Stat6-deficient T cells survived better than wild-type T cells, resulting in higher accumulation in the bronchoalveolar lavage, lung, and lymph nodes. This demonstrates that effector T cell expansion is negatively controlled by a novel Stat6-dependent mechanism which probably serves to limit the number of effector T cells during the acute phase of the immune response and thereby lowers the risk of bystander toxicity against healthy tissues.
Th2细胞是过敏性疾病和寄生虫感染过程中的重要效应细胞。Th2细胞的有效分化需要通过白细胞介素-4受体（IL-4R）和转录因子Stat6进行信号传导。Stat6进一步参与Th2细胞向肺部的募集，可能是记忆性Th2细胞存活所必需的。我们使用竞争性过继转移实验和感染巴西日圆线虫这种蠕虫寄生虫，分析了Stat6在T细胞扩增、存活及向肺部募集中的作用。体内产生的Th2细胞向肺部募集在T细胞或其他细胞类型中并不需要Stat6。对Th2记忆细胞的功能分析显示，CD4 T细胞中的Stat6信号传导对于记忆细胞的产生、扩增和细胞因子分泌并非必需。然而，Stat6缺陷型T细胞比野生型T细胞存活得更好，导致在支气管肺泡灌洗、肺和淋巴结中的积累更高。这表明效应T细胞的扩增受到一种新的Stat6依赖性机制的负调控，该机制可能在免疫反应急性期限制效应T细胞的数量，从而降低对健康组织产生旁观者毒性的风险。
