Bégaud Evélyne, Chartier Loïc, Marechal Valéry, Ipero Julienne, Léal Josianne, Versmisse Pierre, Breton Guillaume, Fontanet Arnaud, Capoulade-Metay Corinne, Fleury Hervé, Barré-Sinoussi Françoise, Scott-Algara Daniel, Pancino Gianfranco
Institut Pasteur, Bangui, CAR.
Retrovirology. 2006 Jun 22;3:35. doi: 10.1186/1742-4690-3-35.
Environmentally driven immune activation was suggested to contribute to high rates of HIV-1 infection in Africa. We report here a study of immune activation markers and susceptibility to HIV-1 infection in vitro of forty-five highly exposed uninfected partners (EUs) of HIV-1 infected individuals in Central African Republic, in comparison with forty-four low-risk blood donors (UCs).
Analysis of T lymphocyte subsets and activation markers in whole blood showed that the absolute values and the percentage of HLA-DR+CD4 T cells and of CCR5+CD4 T cells were lower in the EUs than in the UCs (p = 0.0001). Mutations in the CCR5 coding region were not found in either group. Susceptibility to in vitro infection of unstimulated peripheral blood mononuclear cells, prior of PHA activation, was decreased in EUs compared to UCs, either using a CXCR4-tropic or a CCR5-tropic HIV-1 strain (p = 0.02 and p = 0.05, respectively). Levels of MIP-1beta, but not of MIP-1alpha or RANTES, in the supernatants of PHA-activated PBMC, were higher in the EUs than in the UCs (p = 0.007).
We found low levels of CD4 T cell activation and reduced PBMC susceptibility to HIV-1 infection in Central African EUs, indicating that both may contribute to the resistance to HIV-1 infection.
环境驱动的免疫激活被认为是导致非洲地区HIV-1高感染率的原因之一。我们在此报告一项针对中非共和国45名HIV-1感染者的高暴露未感染伴侣(EUs)的免疫激活标志物及体外HIV-1感染易感性的研究,并与44名低风险献血者(UCs)进行比较。
全血中T淋巴细胞亚群和激活标志物分析显示,EUs中HLA-DR+CD4 T细胞和CCR5+CD4 T细胞的绝对值及百分比均低于UCs(p = 0.0001)。两组均未发现CCR5编码区的突变。与UCs相比,无论是使用CXCR4嗜性还是CCR5嗜性的HIV-1毒株,在PHA激活之前,EUs中未刺激的外周血单核细胞的体外感染易感性均降低(分别为p = 0.02和p = 0.05)。PHA激活的PBMC上清液中MIP-1β水平(而非MIP-1α或RANTES水平)在EUs中高于UCs(p = 0.007)。
我们发现中非EUs中CD4 T细胞激活水平较低,PBMC对HIV-1感染的易感性降低,表明两者均可能有助于抵抗HIV-1感染。