Rac2-deficient mice display perturbed T-cell distribution and chemotaxis, but only minor abnormalities in TH1 responses
Rac2-deficient mice display perturbed T-cell distribution and chemotaxis, but only minor abnormalities in TH1 responses
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DOI：
10.1046/j.1440-1711.2002.01077.x
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发表时间：
2002-06-01
影响因子：
4
通讯作者：
Roberts, AW
中科院分区：
文献类型：
--
作者：
Croker, BA;Handman, E;Roberts, AW
造血细胞特异性RhoGTP酶rac2间接参与T淋巴细胞的发育和功能，并作为T辅助细胞1(T(H)1)应答的关键调节因子。在其他造血细胞中，它调节细胞外信号下游的细胞骨架重排。在这里，我们证明，在体内，缺乏rac2会导致T淋巴细胞的异常分布，并在体外导致T淋巴细胞迁移和丝状肌动蛋白生成对化学诱导剂的反应出现缺陷。为了研究小鼠体内对rac2产生干扰素-γ和T(H)1应答的需求，用大利什曼原虫攻击rac2基因缺陷小鼠，并用表达卵蛋白的巨细胞病毒免疫小鼠。尽管有轻微的向T(H)2表型倾斜，但rac2基因缺陷的小鼠对主要乳杆菌感染的易感性没有增加。对巨细胞病毒和卵蛋白的细胞毒性T淋巴细胞反应也是正常的。虽然rac2是正常T淋巴细胞迁移所必需的，但它在体内对感染产生T(H)1反应中的作用在很大程度上是多余的。
The haematopoietic-specific RhoGTPase, Rac2, has been indirectly implicated in T-lymphocyte development and function, and as a pivotal regulator of T Helper 1 (T(H)1) responses. In other haematopoietic cells it regulates cytoskeletal rearrangement downstream of extracellular signals. Here we demonstrate that Rac2 deficiency results in an abnormal distribution of T lymphocytes in vivo and defects in T-lymphocyte migration and filamentous actin generation in response to chemoattractants in vitro . To investigate the requirement for Rac2 in IFN-gamma production and T(H)1 responses in vivo , Rac2-deficient mice were challenged with Leishmania major and immunized with ovalbumin-expressing cytomegalovirus. Despite a minor skewing towards a T(H)2 phenotype, Rac2-deficient mice displayed no increased susceptibility to L. major infection. Cytotoxic T-lymphocyte responses to cytomegalovirus and ovalbumin were also normal. Although Rac2 is required for normal T-lymphocyte migration, its role in the generation of T(H)1 responses to infection in vivo is largely redundant.