Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, 10 Center Drive, Bethesda, MD 20892, USA.
J Virol. 2011 Jun;85(12):5880-8. doi: 10.1128/JVI.02643-10. Epub 2011 Apr 6.
During acute human immunodeficiency virus (HIV) infection, there is a massive depletion of CD4(+) T cells in the gut mucosa that can be reversed to various degrees with antiretroviral therapy. Th17 cells have been implicated in mucosal immunity to extracellular bacteria, and preservation of this subset may support gut mucosal immune recovery. However, this possibility has not yet been evaluated in HIV-1-infected long-term nonprogressors (LTNPs), who maintain high CD4(+) T cell counts and suppress viral replication in the absence of antiretroviral therapy. In this study, we evaluated the immunophenotype and function of CD4(+) T cells in peripheral blood and gut mucosa of HIV-uninfected controls, LTNPs, and HIV-1-infected individuals treated with prolonged antiretroviral therapy (ART) (VL [viral load]<50). We found that LTNPs have intact CD4(+) T cell populations, including Th17 and cycling subsets, in the gut mucosa and a preserved T cell population expressing gut homing molecules in the peripheral blood. In addition, we observed no evidence of higher monocyte activation in LTNPs than in HIV-infected (HIV(-)) controls. These data suggest that, similar to nonpathogenic simian immunodeficiency virus (SIV) infection, LTNPs preserve the balance of CD4(+) T cell populations in blood and gut mucosa, which may contribute to the lack of disease progression observed in these patients.
在急性人类免疫缺陷病毒 (HIV) 感染期间,肠道黏膜中的 CD4(+) T 细胞大量耗竭,通过抗逆转录病毒治疗可在一定程度上逆转。Th17 细胞已被牵涉到针对细胞外细菌的黏膜免疫中,而这种亚群的保留可能支持肠道黏膜免疫的恢复。然而,这一可能性尚未在 HIV-1 感染的长期非进展者 (LTNPs) 中得到评估,这些患者在未接受抗逆转录病毒治疗的情况下维持高 CD4(+) T 细胞计数并抑制病毒复制。在这项研究中,我们评估了 HIV 未感染对照者、LTNPs 和接受长期抗逆转录病毒治疗 (ART) (VL [病毒载量] < 50) 的 HIV-1 感染者外周血和肠道黏膜中 CD4(+) T 细胞的免疫表型和功能。我们发现,LTNPs 的肠道黏膜中具有完整的 CD4(+) T 细胞群体,包括 Th17 和循环亚群,外周血中表达肠道归巢分子的 T 细胞群体也得到了保留。此外,我们没有观察到 LTNPs 中的单核细胞激活程度高于 HIV 感染 (HIV(-)) 对照者。这些数据表明,与非致病性猴免疫缺陷病毒 (SIV) 感染相似,LTNPs 保留了血液和肠道黏膜中 CD4(+) T 细胞群体的平衡,这可能有助于解释这些患者中观察到的疾病进展缺乏。