Kirsty R Field, Kathleen M Wragg, Stephen J Kent, Wen Shi Lee, Jennifer A Juno
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We additionally explore the <i>in vitro</i> expansion of Vδ2 T cells from PLWH on ART and the mechanisms by which such expanded cells may sense and kill HIV-infected targets.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A matured NK cell-like phenotype was observed for Vδ1 T cells among 25 ART-treated individuals (PLWH/ART) studied compared to 17 HIV-uninfected controls, with heightened expression of 2B4, CD160, TIGIT and Tim-3. Despite persistent phenotypic perturbations, Vδ1 T cells from PLWH/ART exhibited strong CD16-mediated activation and degranulation, which were suppressed upon Tim-3 and TIGIT crosslinking. Vδ2 T cell degranulation responses to the phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate at concentrations up to 2 ng mL<sup>−1</sup> were significantly impaired in an immune checkpoint-independent manner among ART-treated participants. Nonetheless, expanded Vδ2 T cells from PLWH/ART retained potent anti-HIV effector functions, with the NKG2D receptor contributing substantially to the elimination of infected cells.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our findings highlight that although significant perturbations remain within the γδ T cell compartment throughout ART-treated HIV, both subsets retain the capacity for robust anti-HIV effector functions.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 2","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1486","citationCount":"0","resultStr":"{\"title\":\"γδ T cells mediate robust anti-HIV functions during antiretroviral therapy regardless of immune checkpoint expression\",\"authors\":\"Kirsty R Field, Kathleen M Wragg, Stephen J Kent, Wen Shi Lee, Jennifer A Juno\",\"doi\":\"10.1002/cti2.1486\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>Although antiretroviral therapy (ART) efficiently suppresses HIV viral load, immune dysregulation and dysfunction persist in people living with HIV (PLWH). γδ T cells are functionally impaired during untreated HIV infection, but the extent to which they are reconstituted upon ART is currently unclear.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Utilising a cohort of ART-treated PLWH, we assessed the frequency and phenotype, characterised <i>in vitro</i> functional responses and defined the impact of immune checkpoint marker expression on effector functions of both Vδ1 and Vδ2 T cells. We additionally explore the <i>in vitro</i> expansion of Vδ2 T cells from PLWH on ART and the mechanisms by which such expanded cells may sense and kill HIV-infected targets.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>A matured NK cell-like phenotype was observed for Vδ1 T cells among 25 ART-treated individuals (PLWH/ART) studied compared to 17 HIV-uninfected controls, with heightened expression of 2B4, CD160, TIGIT and Tim-3. Despite persistent phenotypic perturbations, Vδ1 T cells from PLWH/ART exhibited strong CD16-mediated activation and degranulation, which were suppressed upon Tim-3 and TIGIT crosslinking. Vδ2 T cell degranulation responses to the phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate at concentrations up to 2 ng mL<sup>−1</sup> were significantly impaired in an immune checkpoint-independent manner among ART-treated participants. Nonetheless, expanded Vδ2 T cells from PLWH/ART retained potent anti-HIV effector functions, with the NKG2D receptor contributing substantially to the elimination of infected cells.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Our findings highlight that although significant perturbations remain within the γδ T cell compartment throughout ART-treated HIV, both subsets retain the capacity for robust anti-HIV effector functions.</p>\\n </section>\\n </div>\",\"PeriodicalId\":152,\"journal\":{\"name\":\"Clinical & Translational Immunology\",\"volume\":\"13 2\",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-01-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1486\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical & Translational Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cti2.1486\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical & Translational Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cti2.1486","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的 虽然抗逆转录病毒疗法(ART)能有效抑制 HIV 病毒载量,但 HIV 感染者(PLWH)的免疫调节紊乱和功能障碍依然存在。在未经治疗的 HIV 感染期间,γδ T 细胞功能受损,但目前尚不清楚抗逆转录病毒疗法后γδ T 细胞的重建程度。 方法 我们利用一组接受抗逆转录病毒疗法治疗的 PLWH,评估了 Vδ1 和 Vδ2 T 细胞的频率和表型、体外功能反应特征,并确定了免疫检查点标记表达对效应功能的影响。此外,我们还探索了抗逆转录病毒疗法治疗的 PLWH 的 Vδ2 T 细胞的体外扩增,以及这种扩增细胞感知和杀伤 HIV 感染目标的机制。 结果 在研究的 25 名接受抗逆转录病毒疗法(ART)治疗的患者(PLWH/ART)与 17 名未受 HIV 感染的对照组相比,观察到 Vδ1 T 细胞具有成熟的 NK 细胞样表型,2B4、CD160、TIGIT 和 Tim-3 表达增强。尽管存在持续的表型扰动,但来自 PLWH/ART 的 Vδ1 T 细胞表现出强烈的 CD16 介导的活化和脱颗粒,在 Tim-3 和 TIGIT 交联后,活化和脱颗粒受到抑制。在接受抗逆转录病毒疗法的参与者中,Vδ2 T细胞对浓度高达2 ng mL-1的磷酸抗原(E)-4-羟基-3-甲基丁-2-烯基焦磷酸的脱颗粒反应明显减弱,这种反应与免疫检查点无关。然而,PLWH/ART 扩增的 Vδ2 T 细胞仍具有强大的抗 HIV 效应功能,其中 NKG2D 受体在消除感染细胞方面做出了重大贡献。 结论 我们的研究结果表明,虽然在抗逆转录病毒疗法治疗的艾滋病毒感染者中,γδ T 细胞区仍存在明显的紊乱,但这两个亚群仍具有强大的抗艾滋病毒效应功能。
γδ T cells mediate robust anti-HIV functions during antiretroviral therapy regardless of immune checkpoint expression
Objectives
Although antiretroviral therapy (ART) efficiently suppresses HIV viral load, immune dysregulation and dysfunction persist in people living with HIV (PLWH). γδ T cells are functionally impaired during untreated HIV infection, but the extent to which they are reconstituted upon ART is currently unclear.
Methods
Utilising a cohort of ART-treated PLWH, we assessed the frequency and phenotype, characterised in vitro functional responses and defined the impact of immune checkpoint marker expression on effector functions of both Vδ1 and Vδ2 T cells. We additionally explore the in vitro expansion of Vδ2 T cells from PLWH on ART and the mechanisms by which such expanded cells may sense and kill HIV-infected targets.
Results
A matured NK cell-like phenotype was observed for Vδ1 T cells among 25 ART-treated individuals (PLWH/ART) studied compared to 17 HIV-uninfected controls, with heightened expression of 2B4, CD160, TIGIT and Tim-3. Despite persistent phenotypic perturbations, Vδ1 T cells from PLWH/ART exhibited strong CD16-mediated activation and degranulation, which were suppressed upon Tim-3 and TIGIT crosslinking. Vδ2 T cell degranulation responses to the phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate at concentrations up to 2 ng mL−1 were significantly impaired in an immune checkpoint-independent manner among ART-treated participants. Nonetheless, expanded Vδ2 T cells from PLWH/ART retained potent anti-HIV effector functions, with the NKG2D receptor contributing substantially to the elimination of infected cells.
Conclusion
Our findings highlight that although significant perturbations remain within the γδ T cell compartment throughout ART-treated HIV, both subsets retain the capacity for robust anti-HIV effector functions.
期刊介绍:
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.