Gulzar Naveed, Balasubramanian Sowyma, Harris Greg, Sanchez-Dardon Jaime, Copeland Karen F T
National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Canada.
Open AIDS J. 2008;2:43-57. doi: 10.2174/1874613600802010043. Epub 2008 Jul 10.
CD8+ T-cells are involved in controlling HIV-1 infection by eliminating infected cells and secreting soluble factors that inhibit viral replication. To investigate the mechanism and significance of infection of CD8+ T-cells by HIV-1 in vitro, we examined the susceptibility of these cells and their subsets to infection. CD8+ T-cells supported greater levels of replication with T-cell tropic strains of HIV-1, though viral production was lower than that observed in CD4+ T-cells. CD8+ T-cell infection was found to be productive through ELISA, RT-PCR and flow cytometric analyses. In addition, the CD8+CD45RO+ memory T-cell population supported higher levels of HIV-1 replication than CD8+CD45RA+ naïve T-cells. However, infection of CD8+CD45RO+ T-cells did not affect their proliferative response to the majority of mitogens tested. We conclude, with numerous lines of evidence detecting and measuring infection of CD8+ T-cells and their subsets, that this cellular target and potential reservoir may be central to HIV-1 pathogenesis.
CD8 + T细胞通过清除被感染细胞和分泌抑制病毒复制的可溶性因子参与控制HIV - 1感染。为了在体外研究HIV - 1感染CD8 + T细胞的机制及意义,我们检测了这些细胞及其亚群对感染的易感性。CD8 + T细胞对HIV - 1的T细胞嗜性毒株支持更高水平的复制,尽管病毒产生量低于在CD4 + T细胞中观察到的水平。通过ELISA、RT - PCR和流式细胞术分析发现CD8 + T细胞感染具有活性。此外,CD8 + CD45RO + 记忆T细胞群体比CD8 + CD45RA + 初始T细胞支持更高水平的HIV - 1复制。然而,CD8 + CD45RO + T细胞的感染并不影响它们对大多数测试有丝分裂原的增殖反应。我们通过检测和测量CD8 + T细胞及其亚群感染的大量证据得出结论,这个细胞靶点和潜在储存库可能是HIV - 1发病机制的核心。