Alvarez Yelina, Tuen Michael, Nàdas Arthur, Hioe Catarina E
Department of Pathology, New York University School of Medicine, New York, New York, USA.
AIDS Res Hum Retroviruses. 2012 Aug;28(8):823-34. doi: 10.1089/AID.2011.0184. Epub 2011 Dec 1.
The Th17 subset is preferentially depleted as compared to the Th1 subset in chronically HIV-infected patients, even after successful antiretroviral therapy. In this study, we have established an in vitro system utilizing primary human CD4 T cell cultures that recapitulates the dramatic loss of Th17 response upon HIV-1 infection that is accompanied with a less profound Th1 decrease. With this experimental system, we showed that blocking viral entry with CCR5 ligands or TAK779 reduced the infection and enhanced Th17 response but not Th1 response. Antiretroviral drug 3TC (lamivudine), given at the time of infection, completely prevented the loss of Th17 and Th1 responses but was ineffective when given after infection was already established. Only when Th17 differentiation cytokines were given along with 3TC to the cultures with established HIV infection was Th17 response fully restored and virus replication kept suppressed. Finally, a significant increase of Th17 response was achieved in peripheral lymphocytes of HIV-infected patients on antiretroviral therapy after treatment with Th17 differentiation cytokines. These data demonstrate the presence of CD4 T cells remaining capable of mounting Th17 response during HIV infection and indicate the potential use of immunotherapeutic modalities to supplement antiretroviral drugs for restoring Th17 response in chronically HIV-infected patients.
与Th1亚群相比，慢性HIV感染患者的Th17亚群即使在抗逆转录病毒治疗成功后也会优先减少。在本研究中，我们利用原代人CD4 T细胞培养建立了一种体外系统，该系统重现了HIV-1感染后Th17反应的显著丧失，同时伴随着Th1反应的较小程度下降。通过这个实验系统，我们发现用CCR5配体或TAK779阻断病毒进入可减少感染并增强Th17反应，但不增强Th1反应。在感染时给予抗逆转录病毒药物3TC（拉米夫定）可完全防止Th17和Th1反应的丧失，但在感染已经确立后给予则无效。只有在已建立HIV感染的培养物中，将Th17分化细胞因子与3TC一起给予时，Th17反应才能完全恢复，病毒复制也能得到抑制。最后，在接受抗逆转录病毒治疗的HIV感染患者的外周淋巴细胞中，用Th17分化细胞因子治疗后，Th17反应显著增加。这些数据表明，在HIV感染期间存在仍能产生Th17反应的CD4 T细胞，并表明免疫治疗方法有可能补充抗逆转录病毒药物，以恢复慢性HIV感染患者的Th17反应。
