Lécuroux Camille, Girault Isabelle, Boutboul François, Urrutia Alejandra, Goujard Cécile, Meyer Laurence, Lambotte Olivier, Chaix Marie-Laure, Martinez Valérie, Autran Brigitte, Sinet Martine, Venet Alain
INSERM U 802, Université Paris-Sud XI, AP-HP Hôpital Bicêtre, Le Kremlin Bicêtre, France.
AIDS. 2009 Aug 24;23(13):1649-58. doi: 10.1097/QAD.0b013e32832e6634.
HIV-specific CD8+ T cells from patients with primary HIV infection (PHI) and after antiretroviral therapy initiation were evaluated for CD127 expression and proliferative capacity and were compared with cells from chronically-infected patients, including long-term nonprogressors and HIV controllers.
We studied 30 patients with PHI (from the Agence Nationale de Recherche sur le SIDA Primo-infection Cohort) and 33 patients with chronic HIV infection (including nonprogressor patients from the Agence Nationale de Recherche sur le SIDA ALT Cohort and the Agence Nationale de Recherche sur le SIDA HIV Controllers Study Group). HIV-specific CD8+ T cells were identified by costaining with HIV human leukocyte antigen class I pentamers. CD127 expression was assessed by flow cytometry and cell proliferation by carboxyfluorescein succinimidyl ester labeling.
During PHI, most HIV-specific CD8+ T cells coexpressed CD27 and CD45RO, were highly activated, and showed weak Bcl-2 expression. Their CD127 expression was very low and correlated negatively both with HIV RNA and DNA levels and with expression of the activation marker CD38. CD127 expression correlated positively with CD4 cell count, Bcl-2 expression and proliferative capacity. Strong CD127 expression was observed in the two groups of chronically-infected nonprogressors. CD127 expression on HIV-specific CD8+ T cells increased in early-treated PHI patients, reaching levels similar to those observed in nonprogressors. In parallel, these cells acquired strong proliferative capacity. No change in CD127 expression or proliferative potential was observed in untreated patients.
Early antiretroviral therapy initiation enhances CD127 expression on HIV-specific CD8+ T cells, reaching levels similar to those observed in aviremic nonprogressors, and restores their proliferative capacity.
评估原发性HIV感染(PHI)患者及开始抗逆转录病毒治疗后的HIV特异性CD8+T细胞的CD127表达和增殖能力,并与慢性感染患者(包括长期无进展者和HIV控制者)的细胞进行比较。
我们研究了30例PHI患者(来自法国国家艾滋病研究机构原发性感染队列)和33例慢性HIV感染患者(包括来自法国国家艾滋病研究机构ALT队列的无进展患者以及法国国家艾滋病研究机构HIV控制者研究组)。通过与HIV I类人白细胞抗原五聚体共染色来鉴定HIV特异性CD8+T细胞。通过流式细胞术评估CD127表达,通过羧基荧光素琥珀酰亚胺酯标记评估细胞增殖。
在PHI期间,大多数HIV特异性CD8+T细胞共表达CD27和CD45RO,高度活化,且Bcl-2表达较弱。它们的CD127表达非常低,与HIV RNA和DNA水平以及活化标志物CD38的表达均呈负相关。CD127表达与CD4细胞计数、Bcl-2表达和增殖能力呈正相关。在两组慢性感染的无进展者中观察到强CD127表达。在早期接受治疗的PHI患者中,HIV特异性CD8+T细胞上的CD127表达增加,达到与无进展者中观察到的水平相似。同时,这些细胞获得了强大的增殖能力。在未治疗的患者中未观察到CD127表达或增殖潜能的变化。
早期开始抗逆转录病毒治疗可增强HIV特异性CD8+T细胞上的CD127表达,达到与病毒血症阴性无进展者中观察到的水平相似,并恢复其增殖能力。