Enhanced development of CD4+ γδ T cells in the absence of Itk results in elevated IgE production
Enhanced development of CD4+ γδ T cells in the absence of Itk results in elevated IgE production
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DOI：
10.1182/blood-2008-12-196345
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发表时间：
2009-07-16
期刊：
影响因子：
20.3
通讯作者：
August, Avery
中科院分区：
文献类型：
--
作者：
Qi, Qian;Xia, Mingcan;August, Avery
Tec激酶Itk对于α β T细胞的发育以及CD 4（+）T细胞分化为Th 2细胞至关重要。Itk基因敲除小鼠在Th 2细胞因子的产生方面有缺陷;然而，它们矛盾地在血清IgE中有显著升高。在这里，我们表明，Itk基因敲除小鼠的胸腺和脾脏中的α δ T细胞数量增加。这包括CD 4（+）α δ T细胞数量增加，其中大多数携带具有不同表型的V γ 1.1和V δ 6.2/3 γ δ T细胞受体。这些CD 4（+）γ δ T细胞的发育是T细胞内在的，独立于主要组织相容性复合物I类或II类，并且在Itk不存在的情况下在发育期间是有利的。Itk无效的CD 4（+）γ δ T细胞分泌显著量的Th 2细胞因子，并且可以诱导野生型B细胞分泌IgE。我们的数据表明Itk在调节γ δ T细胞发育和功能中起重要作用。此外，我们的数据表明，在Itk缺陷小鼠中观察到的IgE升高部分是由于缺乏Itk时CD 4（+）γ δ T细胞的发育增强。（血。2009; 114：564-571）
The Tec kinase Itk is critical for the development of alpha beta T cells as well as differentiation of CD4(+) T cells into Th2 cells. Itk null mice have defects in the production of Th2 cytokines; however, they paradoxically have significant elevations in serum IgE. Here we show that Itk null mice have increased numbers of alpha delta T cells in the thymus and spleen. This includes elevated numbers of CD4(+) alpha delta T cell, the majority of which carry the V gamma 1.1 and V delta 6.2/3 gamma delta T-cell receptor with a distinct phenotype. The development of these CD4(+) gamma delta T cells is T cell intrinsic, independent of either major histocompatibility complex class I or class II, and is favored during development in the absence of Itk. Itk null CD4(+) gamma delta T cells secrete significant amounts of Th2 cytokines and can induce the secretion of IgE by wild-type B cells. Our data indicate that Itk plays important role in regulating gamma delta T-cell development and function. In addition, our data indicate that the elevated IgE observed in Itk-deficient mice is due in part to the enhanced development of CD4(+) gamma delta T cells in the absence of Itk. (Blood. 2009; 114: 564-571)