The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection.
The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection.
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DOI：
10.4049/jimmunol.1202448
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发表时间：
2013-01-15
期刊：
影响因子：
--
通讯作者：
Whitmire JK
中科院分区：
文献类型：
--
作者：
Cook KD;Whitmire JK
自然杀伤细胞通过其溶细胞活性和产生细胞因子，在对抗病毒感染和癌症的免疫防御中具有广泛的功能。在这里，我们检测了NK细胞的频率以及它们对淋巴细胞脉络膜脑膜炎病毒(LCMV)变异的小鼠T细胞反应的影响。我们发现，与未感染或急性感染的小鼠相比，在传播性感染期间循环中NK细胞的频率增加。与最近的报道一致，我们观察到，在播散性感染的小鼠中，NK细胞的耗尽增加了产生CD8+T细胞的病毒特异性细胞因子的峰值数量，并导致播散性感染迅速消退。此外，我们还发现，自然杀伤细胞耗竭维持T细胞反应，并保护T细胞免于耗尽。只有当NK细胞在感染的前两天内被耗尽时，NK细胞耗尽才会对T细胞应答产生积极影响。我们发现，CD8+T细胞反应的改善与来自NK细胞耗竭小鼠的APC刺激T细胞增殖的能力增强相关，与NK细胞对CD4+T细胞的影响无关。这些结果表明，NK细胞在限制CD8 T细胞应答中发挥着不可或缺的作用，并在病毒持续感染过程中通过降低APC功能而导致T细胞耗竭。
Natural killer cells have well-established functions in immune defense against virus infections and cancer through their cytolytic activity and production of cytokines. Herein, we examined the frequency of NK cells and their influence on T cell responses in mice given variants of lymphocytic choriomeningitis virus (LCMV) that cause acute or persisting infection. We found increased frequencies of circulating NK cells during disseminating infection compared to uninfected or acutely infected mice. Consistent with recent reports, we observed that the depletion of NK cells in mice with disseminated infection increased peak numbers of virus-specific cytokine producing CD8+ T cells and resulted in the rapid resolution of disseminated infection. Additionally, we show that NK cell depletion sustained T cell responses across time and protected against T cell exhaustion. The positive effects of NK cell depletion on T cell responses only occurred when NK cells were depleted within the first two days of infection. We find that the improved CD8+ T cell response correlated with an enhanced ability of APCs from NK cell-depleted mice to stimulate T cell proliferation, independently of the effects of NK cells on CD4+ T cells. These results indicate that NK cells play an integral role in limiting the CD8 T cell response and contribute to T cell exhaustion by diminishing APC function during persisting virus infection.
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DOI：
10.1084/jem.20010938
发表时间：
2002-02-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gerosa F;Baldani-Guerra B;Nisii C;Marchesini V;Carra G;Trinchieri G
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OLDSTONE, MBA
影响因子：
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作者：
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