Generation and characterization of B7-H4/B7S1/B7x-deficient mice
Generation and characterization of B7-H4/B7S1/B7x-deficient mice
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DOI：
10.1128/mcb.00755-06
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发表时间：
2006-09-01
影响因子：
5.3
通讯作者：
Mak, Tak W.
中科院分区：
文献类型：
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作者：
Suh, Woong-Kyung;Wang, Seng;Mak, Tak W.
共信号分子B7家族的成员通过与T细胞上的同源受体结合来调节T细胞的增殖和效应器功能。体外和体内阻断实验表明，B7-H4(也称为B7S1或B7x)可抑制T细胞的增殖、细胞因子的产生和细胞毒作用。B7-H4与一种未知的受体(S)结合，该受体表达在激活的T细胞上。然而，B7-H4在体内是否发挥非多余的免疫调节作用还没有得到测试。我们建立了B7-H4缺陷小鼠，以研究B7-H4在各种免疫反应中的作用。与其体外抑制功能一致，B7-H4缺陷小鼠的T辅助细胞1(Th1)反应略有增强，与野生型小鼠相比，对主要利什曼原虫感染的寄生虫负担略有降低。然而，缺乏B7-H4并不影响由Th1或Th2细胞诱导的呼吸道或皮肤的过敏性炎症反应。同样，B7-H4缺陷小鼠对病毒感染产生了正常的细胞毒性T淋巴细胞反应。因此，B7-H4在体内起着负面调节作用，但B7-H4缺乏的影响微乎其微。这些结果表明，B7-H4是多种负性共信号分子之一，它们共同为T细胞介导的免疫反应提供微调机制。
Members of the B7 family of cosignaling molecules regulate T-cell proliferation and effector functions by engaging cognate receptors on T cells. In vitro and in vivo blockade experiments indicated that B7-H4 (also known as B7S1 or B7x) inhibits proliferation, cytokine production, and cytotoxicity of T cells. B7-H4 binds to an unknown receptor(s) that is expressed on activated T cells. However, whether B7-H4 plays nonredundant immune regulatory roles in vivo has not been tested. We generated B7-H4-deficient mice to investigate the roles of B7-H4 during various immune reactions. Consistent with its inhibitory function in vitro, B7-H4-deficient mice mounted mildly augmented T-helper 1 (Th1) responses and displayed slightly lowered parasite burdens upon Leishmania major infection compared to the wild-type mice. However, the lack of B7-H4 did not affect hypersensitive inflammatory responses in the airway or skin that are induced by either Thl or Th2 cells. Likewise, B7-H4-deficient mice developed normal cytotoxic T-lymphocyte reactions against viral infection. Thus, B7-H4 plays a negative regulatory role in vivo but the impact of B7-H4 deficiency is minimal. These results suggest that B7-H4 is one of multiple negative cosignaling molecules that collectively provide a fine-tuning mechanism for T-cell-mediated immune responses.