CD4+ T Cells, Including Th17 and Cycling Subsets, Are Intact in the Gut Mucosa of HIV-1-Infected Long-Term Nonprogressors
CD4+ T Cells, Including Th17 and Cycling Subsets, Are Intact in the Gut Mucosa of HIV-1-Infected Long-Term Nonprogressors
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DOI：
10.1128/jvi.02643-10
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Sereti, Irini
中科院分区：
文献类型：
--
作者：
Ciccone, Emily J.;Greenwald, Jamieson H.;Sereti, Irini
在急性人类免疫缺陷病毒（HIV）感染期间，肠道粘膜中的CD4（+）T细胞大量减少，抗逆转录病毒治疗可以不同程度地逆转这种情况。 Th17 细胞与细胞外细菌的粘膜免疫有关，保留该亚群可能支持肠道粘膜免疫恢复。然而，这种可能性尚未在HIV-1感染的长期无进展者（LTNP）中得到评估，这些人在没有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。在本研究中，我们评估了未感染 HIV 的对照、LTNP 和接受长期抗逆转录病毒治疗 (ART)（VL [病毒载量] < 50）治疗的 HIV-1 感染者的外周血和肠粘膜中 CD4(+) T 细胞的免疫表型和功能。我们发现LTNPs在肠粘膜中具有完整的CD4+T细胞群，包括Th17和循环亚群，并且在外周血中保留表达肠道归巢分子的T细胞群。此外，我们没有观察到 LTNP 中单核细胞活化程度高于 HIV 感染者 (HIV-) 对照的证据。这些数据表明，与非致病性猿猴免疫缺陷病毒（SIV）感染类似，LTNP 可以保持血液和肠道粘膜中 CD4（+）T 细胞群的平衡，这可能导致在这些患者中观察到疾病进展不足。
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.