Weak vaccinia virus-induced NK cell regulation of CD4 T cells is associated with reduced NK cell differentiation and cytolytic activity.

Weak vaccinia virus-induced NK cell regulation of CD4 T cells is associated with reduced NK cell differentiation and cytolytic activity.
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DOI:
10.1016/j.virol.2018.04.012
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发表时间:
2018-06
期刊:
影响因子:
3.7
通讯作者:
Welsh RM
Welsh RM
中科院分区:
医学3区
文献类型:
--
作者:
Hatfield SD;Daniels KA;O'Donnell CL;Waggoner SN;Welsh RM

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自然杀伤(NK)细胞在某些病毒感染期间控制小鼠的抗病毒适应性免疫反应,但这种现象的普遍性仍然未知。小鼠淋巴细胞性脉络丛脑膜炎病毒(LCMV)感染引发NK细胞(NKLCMV)对活化的CD 4 T细胞、肿瘤细胞和同种异体淋巴细胞的强效细胞毒活性。相比之下,由牛痘病毒(VACV)感染(NKVACV)激活的NK细胞对这些靶细胞中的每一种表现出较弱的细胞溶解活性。相对于NKLCMV细胞,NKVACV细胞表现出更不成熟(CD 11 b-CD 27+)的表型,活化标志物CD 69、细胞毒性效应分子(穿孔素、颗粒酶B)和转录因子IRF 4的表达水平较低。NKVACV细胞比NKLCMV细胞表达更高水平的抑制分子NKG 2A。与这种明显的嗜睡相一致,NKVacv细胞仅微弱地抑制VACV特异性CD 4 T细胞应答。这表明NK细胞对适应性免疫的调节虽然是普遍的,但可能受到激活NK细胞能力差的病毒的限制。
Natural killer (NK) cells control antiviral adaptive immune responses in mice during some virus infections, but the universality of this phenomenon remains unknown. Lymphocytic choriomeningitis virus (LCMV) infection of mice triggered potent cytotoxic activity of NK cells (NKLCMV) against activated CD4 T cells, tumor cells, and allogeneic lymphocytes. In contrast, NK cells activated by vaccinia virus (VACV) infection (NKVACV) exhibited weaker cytolytic activity against each of these target cells. Relative to NKLCMV cells, NKVACV cells exhibited a more immature (CD11b-CD27+) phenotype, and lower expression levels of the activation marker CD69, cytotoxic effector molecules (perforin, granzyme B), and the transcription factor IRF4. NKVACV cells expressed higher levels of the inhibitory molecule NKG2A than NKLCMV cells. Consistent with this apparent lethargy, NKVacv cells only weakly constrained VACV-specific CD4 T-cell responses. This suggests that NK cell regulation of adaptive immunity, while universal, may be limited with viruses that poorly activate NK cells.
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