Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk
Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk
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DOI：
10.1016/j.immuni.2006.05.011
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发表时间：
2006-07-01
期刊：
影响因子：
32.4
通讯作者：
Schwartzberg, Pamela L.
中科院分区：
文献类型：
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作者：
Broussard, Christine;Fleischecker, Christine;Schwartzberg, Pamela L.
影响Tec激酶Itk和Rlk的突变降低T细胞受体诱导的Ca 2+动员和Erk激酶活化，并损害阳性和阴性胸腺选择。Itk（-/-）和Rlk（-/-）Itk（-/-）小鼠也具有降低的CD 4：8 T细胞比率，提示改变的CD 4：8谱系定型。尽管如此，我们发现这些小鼠的CD 8单阳性（SP）胸腺细胞和外周CD 8（+）T细胞并不像传统的CD 8（+）T细胞。相反，这些细胞表达记忆标记，快速产生干扰素-γ，并且可以在造血衍生细胞上被选择，类似于MHC Ib类限制性“先天型”淋巴细胞。Itk缺陷也大大增加了由MHC Ib类选择的细胞的数量。一种超敏Erk 2突变体的表达部分纠正了Itk（-/-）小鼠中的CD 8（+）T细胞表型，认为改变的信号传导允许这种先天型CD 8（+）细胞群的发育。我们的研究结果表明，Tec激酶差异调节常规与非常规淋巴细胞的发展。
Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection. Itk(-/-) and Rlk(-/-) Itk(-/-) mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8(+) T cells in these mice do not resemble conventional CD8(+) T cells. Instead, these cells express memory markers, rapidly produce interferon-gamma, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted "innate-type" lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8(+) T cell phenotypes in Itk(-/-) mice, arguing that altered signaling permits development of this innate-type CD8(+) cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes.