NK cells inhibit humoral immunity by reducing the abundance of CD4+ T follicular helper cells during a chronic virus infection
NK cells inhibit humoral immunity by reducing the abundance of CD4+ T follicular helper cells during a chronic virus infection
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DOI：
10.1189/jlb.4hi1214-594r
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发表时间：
2015-08-01
影响因子：
5.5
通讯作者：
Whitmire, Jason K.
中科院分区：
文献类型：
--
作者：
Cook, Kevin D.;Kline, Hannah C.;Whitmire, Jason K.
有必要更好地了解如何提高B细胞对持续病毒感染的反应和免疫力，这种病毒感染通常会导致虚弱的疾病或死亡。当有强烈的中和抗体反应时，慢性病毒感染者表现出改善病毒控制的证据，反之，B细胞功能障碍与较高的病毒载量有关。我们以前发现，NK细胞抑制CD4(+)和CD8(+)T细胞对传播LCMV感染的反应，而NK细胞的耗尽可以减轻慢性感染。在这里，我们研究了NK细胞耗尽对小鼠对LCMV感染的B细胞反应的影响。虽然急性感染的小鼠在感染缓解后不久就产生了抗体水平的峰值，但长期感染的小鼠的抗体水平持续上升，超过了急性感染后的水平。我们发现，早期NK细胞耗尽会迅速增加针对慢性感染的病毒特异性抗体水平，这一效应依赖于CD4(+)T细胞，并与CXCR5(+)CD4(+)T-FH细胞的数量增加有关。然而，NK细胞耗尽的小鼠控制了感染，与持续感染的小鼠相比，1mo pi的T-FH细胞数量和抗体水平较低。最后，我们发现，只有在B细胞和病毒特异性抗体存在的情况下，NK细胞去除才能改善抗病毒CD8(+)T细胞的反应。我们的数据表明，NK细胞通过抑制T-FH细胞和抗体反应部分地降低了对慢性感染的免疫力。
There is a need to understand better how to improve B cell responses and immunity to persisting virus infections, which often cause debilitating illness or death. People with chronic virus infection show evidence of improved virus control when there is a strong neutralizing antibody response, and conversely, B cell dysfunction is associated with higher viral loads. We showed previously that NK cells inhibit CD4(+) and CD8(+) T cell responses to disseminating LCMV infection and that depletion of NK cells attenuates chronic infection. Here, we examined the effect of NK cell depletion on B cell responses to LCMV infection in mice. Whereas mice infected acutely generated a peak level of antibody soon after the infection was resolved, mice infected chronically showed a continued increase in antibody levels that exceeded those after acute infection. We found that early NK cell depletion rapidly increased virus-specific antibody levels to chronic infection, and this effect depended on CD4(+) T cells and was associated with elevated numbers of CXCR5(+)CD4(+) T-FH cells. However, the NK cell-depleted mice controlled the infection and by 1 mo pi, had lower T-FH cell numbers and antibody levels compared with mice with sustained infection. Finally, we show that NK cell depletion improved antiviral CD8(+) T cell responses only when B cells and virus-specific antibody were present. Our data indicate that NK cells diminish immunity to chronic infection, in part, by suppressing T-FH cell and antibody responses.