Impact of mucosal inflammation on cervical human immunodeficiency virus (HIV-1)-specific CD8 T-cell responses in the female genital tract during chronic HIV infection
Impact of mucosal inflammation on cervical human immunodeficiency virus (HIV-1)-specific CD8 T-cell responses in the female genital tract during chronic HIV infection
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DOI：
10.1128/jvi.00183-08
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发表时间：
2008-09-01
影响因子：
5.4
通讯作者：
Passmore, Jo-Ann S.
中科院分区：
文献类型：
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作者：
Gumbi, Pamela P.;Nkwanyana, Nonhlanhla N.;Passmore, Jo-Ann S.
女性生殖道是人类免疫缺陷病毒（HIV）在异性间感染和传播的主要途径。在这里，我们调查是否可以检测到HIV特异性CD 8 T细胞介导的免疫反应，在生殖器粘膜慢性HIV感染的妇女，以及这些是否与局部粘膜HIV脱落或局部免疫因素。我们发现，在HIV感染妇女的宫颈处可检测到CD 8（+）T细胞γ干扰素对Gag的反应，但生殖器反应的程度与血液中检测到的类似反应无关。这表明一个隔室中的离体HIV应答可能不能预测另一个隔室中的HIV应答。我们发现，生殖器肿瘤坏死因子α（TNF-α）和白细胞介素-10（IL-10）水平的升高与子宫颈处GAG特异性CD 8（+）T细胞的水平显著相关。与未检测到病毒脱落的女性相比，生殖道中可检测到病毒脱落的女性宫颈TNF-α、IL-1 β、IL-6和IL-8水平显著升高。然而，我们无法检测到宫颈HIV特异性反应的幅度与粘膜HIV脱落之间的任何关联。我们的研究结果支持这一假设，即女性生殖道中的促炎细胞因子可能会促进艾滋病毒的复制和脱落。此外，我们进一步表明，炎症细胞因子与生殖器粘膜HIV特异性CD 8效应细胞水平的增加有关，但这些细胞不能控制生殖器HIV脱落。
The female genital tract is the major route of heterosexual human immunodeficiency virus (HIV) acquisition and transmission. Here, we investigated whether HIV-specific CD8 T-cell-mediated immune responses could be detected in the genital mucosa of chronically HIV-infected women and whether these were associated with either local mucosal HIV shedding or local immune factors. We found that CD8(+) T-cell gamma interferon responses to Gag were detectable at the cervix of HIV-infected women but that the magnitude of genital responses did not correlate with those similarly detected in blood. This indicates that ex vivo HIV responses in one compartment may not be predictive of those in the other. We found that increased genital tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) levels correlated significantly with levels of Gag-specific CD8(+) T cells at the cervix. Women who were detectably shedding virus in the genital tract had significantly increased cervical levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 compared to women who were not detectably shedding virus. We were, however, unable to detect any association between the magnitude of cervical HIV-specific responses and mucosal HIV shedding. Our results support the hypothesis that proinflammatory cytokines in the female genital tract may promote HIV replication and shedding. In addition, we further show that inflammatory cytokines are associated with increased levels of HIV-specific CD8 effector cells at the genital mucosa but that these were not able to control genital HIV shedding.