CCR 5 is not only a coreceptor for HIV ‐1 infection in CD 4⁺ T cells, but also contributes to their functional fitness. Here, we show that by limiting transcription of specific ceramide synthases, CCR 5 signaling reduces ceramide levels and thereby increases T‐cell antigen receptor (TCR ) nanoclustering in antigen‐experienced mouse and human CD 4⁺ T cells. This activity is CCR 5‐specific and independent of CCR 5 co‐stimulatory activity. CCR 5‐deficient mice showed reduced production of high‐affinity class‐switched antibodies, but only after antigen rechallenge, which implies an impaired memory CD 4⁺ T‐cell response. This study identifies a CCR 5 function in the generation of CD 4⁺ T‐cell memory responses and establishes an antigen‐independent mechanism that regulates TCR nanoclustering by altering specific lipid species.

中文翻译：

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CCR5缺乏症通过增加的神经酰胺合成而损害CD4 + T细胞记忆反应和抗原敏感性。

CCR 5不仅是CD 4 ⁺ T细胞中HIV -1感染的共受体，而且还有助于它们的功能适应性。在这里，我们表明，通过限制特定神经酰胺合酶的转录，CCR 5信号传导降低了神经酰胺水平，从而增加了抗原经历过的小鼠和人类CD 4 ⁺ T细胞中的T细胞抗原受体（TCR）纳米簇。该活性是CCR 5特异性的，并且独立于CCR 5共刺激活性。CCR 5缺陷小鼠显示出高亲和力的类转换抗体产生减少，但仅在抗原挑战后才出现，这意味着记忆CD 4 ⁺ T细胞反应受损。这项研究确定了CD 4 ⁺产生中的CCR 5功能 T细胞记忆反应并建立了一种独立于抗原的机制，该机制通过改变特定的脂质种类来调节TCR纳米簇。