Impact of rosuvastatin on the memory potential and functionality of CD8⁺ T cells from people with HIV.

IF 9.7 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-03-29 DOI:10.1016/j.ebiom.2025.105672

Federico Perdomo-Celis, Caroline Passaes, Valérie Monceaux, Olivier Lambotte, Dominique Costagliola, Mathieu F Chevalier, Laurence Weiss, Asier Sáez-Cirión

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引用次数: 0

Abstract

Background: Virus-specific CD8⁺ T cells play a major role in the natural control of HIV infection, linked to memory-like features such as high survival capacity and polyfunctionality. However, virus-specific CD8⁺ T cells from HIV non-controllers exhibit an effector-like and exhausted profile, with limited antiviral potential. Metabolic reprogramming of cells from non-controllers could reinvigorate their functional capacities. Considering the implication of the cholesterol pathway in the induction of T cell exhaustion, here we evaluated the impact of rosuvastatin, an inhibitor of cholesterol synthesis, on the functionality and memory profile of HIV-specific CD8⁺ T cells from people on antiretroviral treatment.

Methods: We analysed samples from 10 individuals with HIV-1 on ART who participated in the IMEA 043-CESAR trial and received rosuvastatin for 12 weeks. We explored whether rosuvastatin treatment was accompanied by changes in the memory potential of CD8⁺ T cells. We evaluated the phenotype and functionality of total and HIV-specific CD8⁺ T cells before, during, and after treatment with rosuvastatin. A mixed effects model was used for repeated measures and corrected for multiple comparisons.

Findings: Total and HIV-specific CD8⁺ T cell survival and functionality were enhanced in individuals who received a 12-week course of rosuvastatin, with a consistent increase in polyfunctional IFN-γ⁺ TNF-α⁺ cells. The superior CD8⁺ T cell functionality after rosuvastatin treatment was associated with intrinsic metabolic changes, including the decrease of fatty acid uptake, as well as a reduction in effector/exhaustion markers. Changes in the characteristics of CD8⁺ T cells coincided with the duration of rosuvastatin administration, and most effects waned after the cessation of the treatment.

Interpretation: CD8⁺ T cell metabolic reprogramming by targeting the cholesterol pathway, combined with other available immunotherapies, might represent a promising strategy in the search for the cure of HIV or other chronic viral infections.

Funding: The CESAR trial was sponsored by IMEA. This work was supported by the NIH (grants UM1AI164562 and R01DK131476).

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背景：病毒特异性 CD8+ T 细胞在艾滋病病毒感染的自然控制中发挥着重要作用，这与高存活能力和多功能性等类似记忆的特征有关。然而，来自 HIV 非控制者的病毒特异性 CD8+ T 细胞表现出类似效应器的特征，且已耗竭，抗病毒潜力有限。对来自非控制者的细胞进行新陈代谢重编程可重振其功能能力。考虑到胆固醇途径在诱导 T 细胞衰竭中的作用，我们在此评估了洛伐他汀（一种胆固醇合成抑制剂）对接受抗逆转录病毒治疗者的 HIV 特异性 CD8+ T 细胞的功能和记忆特征的影响：我们分析了 10 名接受抗逆转录病毒疗法的 HIV-1 感染者的样本，他们参加了 IMEA 043-CESAR 试验，并接受了为期 12 周的洛伐他汀治疗。我们探讨了洛伐他汀治疗是否会导致 CD8+ T 细胞的记忆潜能发生变化。我们评估了洛伐他汀治疗前、治疗中和治疗后总CD8+ T细胞和HIV特异性CD8+ T细胞的表型和功能。采用混合效应模型进行重复测量，并进行多重比较校正：研究结果：接受为期12周的洛伐他汀治疗后，总CD8+ T细胞和HIV特异性CD8+ T细胞的存活率和功能均有所提高，多功能IFN-γ+ TNF-α+细胞持续增加。洛伐他汀治疗后 CD8+ T 细胞功能的增强与内在代谢变化有关，包括脂肪酸吸收的减少以及效应/耗竭标记物的减少。CD8+ T细胞特征的变化与洛伐他汀的用药时间一致，大多数影响在停止用药后减弱：解读：通过靶向胆固醇途径对CD8+ T细胞代谢进行重编程，并结合其他可用的免疫疗法，可能是寻求治愈艾滋病或其他慢性病毒感染的一种有前途的策略：CESAR试验由IMEA赞助。这项工作得到了美国国立卫生研究院（UM1AI164562 和 R01DK131476 号基金）的支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.