The mechanisms inducing exhaustion of HIV-specific CD8⁺ T cells are not fully understood. Metabolic programming directly influences T-cell differentiation, effector function, and memory. We evaluated metabolic profiles of ex vivo CD8⁺ T cells in HIV-infected individuals. The baseline oxygen consumption rate of CD8⁺ T cells was elevated in all infected individuals and CD8⁺ T cells were working at maximal respiratory capacity. The baseline glycolysis rate was enhanced only during early untreated HIV and in viral controllers, but glycolytic capacity was conserved at all stages of infection. CD8⁺ T-cell mTOR activity was found to be reduced. Enhanced glycolysis was crucial for HIV-specific killing of CD8⁺ T cells. CD8⁺ T-cell cytoplasmic GAPDH content was reduced in HIV, but less in early infection and viral controllers. Thus, CD8⁺ T-cell exhaustion in HIV is characterized by reduced glycolytic activity, enhanced OXPHOS demands, dysregulated mTOR, and reduced cytoplasmic GAPDH. These data provide potential metabolic strategies to reverse CD8⁺ T-cell dysfunction in HIV.

中文翻译：

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升高的糖酵解赋予 CD8+ T 细胞在 HIV 感染中的功能能力。

诱导 HIV 特异性 CD8 ⁺ T 细胞耗竭的机制尚不完全清楚。代谢程序直接影响 T 细胞分化、效应器功能和记忆。我们评估了 HIV 感染个体的离体 CD8 ⁺ T 细胞的代谢特征。^{所有感染个体的 CD8 +} T 细胞的基线耗氧率均升高，并且 CD8 ⁺ T 细胞以最大呼吸能力工作。基线糖酵解速率仅在早期未经治疗的 HIV 和病毒控制者中增加，但糖酵解能力在感染的所有阶段都保持不变。发现CD8 ⁺ T 细胞 mTOR 活性降低。增强的糖酵解对于 HIV 特异性杀伤 CD8 至关重要⁺ T 细胞。CD8 ⁺ T 细胞细胞质 GAPDH 含量在 HIV 中减少，但在早期感染和病毒控制者中减少。因此，HIV 中 CD8 ⁺ T 细胞衰竭的特征是糖酵解活性降低、OXPHOS 需求增加、mTOR 失调和细胞质 GAPDH 减少。这些数据提供了逆转 HIV 中 CD8 ⁺ T 细胞功能障碍的潜在代谢策略。