Impaired clearance of herpes simplex virus type 1 from mice lacking CD1d or NKT cells expressing the semivariant Vα14-Jα281 TCR

Impaired clearance of herpes simplex virus type 1 from mice lacking CD1d or NKT cells expressing the semivariant Vα14-Jα281 TCR
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DOI:
10.4049/jimmunol.170.3.1430
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发表时间:
2003-02-01
影响因子:
4.4
通讯作者:
Speck, PG
Speck, PG
中科院分区:
医学2区
文献类型:
--
作者:
Grubor-Bauk, B;Simmons, A;Speck, PG

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已知Ag呈递分子CD 1和CD 1限制性NKT细胞有助于防御一系列感染性病原体,包括一些病毒。CD 1限制性NKT细胞是T细胞的一个独特亚群,具有显著和快速的效应功能,有助于宿主防御,包括快速产生IFN-γ和IL-4,以及激活NK细胞。考虑到先天性和适应性免疫对HSV清除的重要贡献,促使我们研究了表达Valpha 14-Jalpha 281 TCR的CD 1和NKT细胞在HSV感染发病机制中的作用。为了解决这个问题,我们比较了野生型小鼠与CD 1基因敲除(GKO)和Jalpha 281 GKO小鼠的感染。在这项研究中,我们报告了与亲代C57 BL 6小鼠相比,缺乏CD 1(并推断为CD 1限制性T细胞)的小鼠中病毒和病毒抗原的清除受损,以及更明显的急性感染。在Ja 281 GKO小鼠中,病毒清除也受到损害,与CD 1 GKO小鼠中观察到的情况类似。这些结果暗示了NKT细胞的Valpha 14-Jalpha 281亚群和CD 1d在控制HSV感染中的作用。
Ag-presenting molecule CD1 and CD1-restricted NKT cells are known to contribute to defense against a range of infectious pathogens, including some viruses. CD1-restrieted NKT cells, a distinct subpopulation of T cells, have striking and rapid effector functions that contribute to host defense, including rapid production of IFN-gamma and IL-4, and activation of NK cells. Consideration of the important contributions of innate and adaptive immunity to clearance of HSV prompted us to investigate the role of CD1 and of NKT cells expressing the Valpha14-Jalpha281 TCR in the pathogenesis of HSV infection. To address this issue, we compared infection in wild-type mice with that in CD1 gene knockout (GKO) and Jalpha281 GKO mice. In this study, we report impaired clearance of virus and viral Ags, and more florid acute infection in mice lacking CD1 (and by inference, CD1-restrieted T cells), in comparison with parental C57BL6 mice. In Ja281 GKO mice there was also impairment of virus clearance, resembling that seen in CD1 GKO mice. These results imply roles for the Valpha14-Jalpha281 subset of NKT cells and for CD1d in control of HSV infection.