Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, United States of America.
PLoS One. 2011;6(11):e28172. doi: 10.1371/journal.pone.0028172. Epub 2011 Nov 29.
Regulatory T cells (Treg) increase in the context of HIV infection and pregnancy. We studied Treg subpopulations in HIV-infected and uninfected women during pregnancy and their relationship with inflammation, activation and cell-mediated immunity (CMI).
Blood obtained from 20 HIV-infected and 18 uninfected women during early and late gestation was used to measure Treg and activated T cells (Tact) by flow cytometry; plasma cytokines and inflammatory markers by ELISA and chemoluminescence; and CMI against varicella-zoster virus (VZV) by lymphocyte proliferation.
Compared with uninfected women, HIV-infected participants had higher frequencies of Treg subpopulations in early pregnancy, including CD4+CD25+FoxP3+%, CD8+CD25+FoxP3+%, CD4+TGFβ+% and CD4+IL10+%. In contrast, Treg frequencies were lower during late pregnancy in HIV-infected compared with uninfected women, including CD8+TGFβ+%, CD4+CTLA4+% and CD8+CTLA4+%. VZV-CMI, which was lower in HIV-infected compared with uninfected pregnant women, was inversely correlated with CD4+FoxP3+%, CD8+FoxP3+% and CD8+TGFβ+% in HIV-infected, but not in uninfected pregnant women. β₂-microglobulin, neopterin, IL1, IL4, IL8, IL10, IFNγ and TNFα plasma concentrations as well as Tact were higher in HIV-infected compared with uninfected women throughout pregnancy. In HIV-infected, but not in uninfected women, inflammatory, Th1, Th2 and regulatory cytokines increased with higher Treg%, suggesting that inflammation and regulation have a common pathophysiologic origin in the context of HIV infection. In HIV-infected and more commonly in uninfected pregnant women, higher Treg% correlated with lower Tact%. We conclude that Treg have different dynamics during pregnancy in HIV-infected and uninfected women. Higher levels of inflammatory cytokines and lower Treg% during late pregnancy in HIV-infected women may contribute to their increased incidence of maternal-fetal morbidity.
调节性 T 细胞（Treg）在 HIV 感染和妊娠期间增加。我们研究了 HIV 感染和未感染孕妇在妊娠期间的 Treg 亚群及其与炎症、激活和细胞介导免疫（CMI）的关系。
从 20 名 HIV 感染和 18 名未感染孕妇的妊娠早期和晚期获得血液，通过流式细胞术测量 Treg 和活化 T 细胞（Tact）；通过 ELISA 和化学发光法测量血浆细胞因子和炎症标志物；通过淋巴细胞增殖测量抗水痘带状疱疹病毒（VZV）的 CMI。
与未感染妇女相比，HIV 感染参与者在妊娠早期具有更高频率的 Treg 亚群，包括 CD4+CD25+FoxP3+%、CD8+CD25+FoxP3+%、CD4+TGFβ+%和 CD4+IL10+%。相比之下，与未感染妇女相比，HIV 感染妇女在妊娠晚期的 Treg 频率较低，包括 CD8+TGFβ+%、CD4+CTLA4+%和 CD8+CTLA4+%。与未感染的孕妇相比，HIV 感染孕妇的 VZV-CMI 较低，与 HIV 感染孕妇的 CD4+FoxP3+%、CD8+FoxP3+%和 CD8+TGFβ+%呈负相关，但与未感染的孕妇无关。β₂-微球蛋白、新蝶呤、IL1、IL4、IL8、IL10、IFNγ和 TNFα 血浆浓度以及 Tact 在整个妊娠期间在 HIV 感染妇女中均高于未感染妇女。在 HIV 感染妇女中，但在未感染妇女中，炎症、Th1、Th2 和调节性细胞因子随着更高的 Treg%而增加，这表明在 HIV 感染的情况下，炎症和调节具有共同的病理生理起源。在 HIV 感染妇女中，更常见的是在未感染的孕妇中，较高的 Treg%与较低的 Tact%相关。我们得出结论，在 HIV 感染和未感染的孕妇中，Treg 在妊娠期间具有不同的动态。在 HIV 感染妇女中，妊娠晚期更高的炎症细胞因子和更低的 Treg%可能导致其母婴发病率增加。
