Jones Norman, Eggena Mark, Baker Chris, Nghania Frehd, Baliruno David, Mugyenyi Peter, Ssali Francis, Barugahare Banson, Cao Huyen
California Department of Health Services, Richmond, California 94804, USA.
AIDS Res Hum Retroviruses. 2006 Oct;22(10):1007-13. doi: 10.1089/aid.2006.22.1007.
Cytolytic T lymphocytes (CTL) play an important role in the control of HIV infection. The eventual failure to contain HIV-1 infection may arise because of a functional impairment of HIV-specific CTL. We evaluated Gag-specific cytotoxicity in HIV-1-positive Ugandans. Expression of CD107, a marker for cytolytic activity, was present in CD45RA(bright) and CD45RA(dim) CD8(+) T cell populations in HIV-infected individuals. The frequency of Gag-specific CD107(+)CD45RA(bright)CD28(-)CCR7(-) CD8(+) T cells decreased with CD4 cell depletion and correlated with the presence of Gag-specific T helper response. In contrast, the frequency of Gag-specific CD107(+)CD45RA(dim)CD28(-)CCR7(-) CD8(+) T cells within the same individuals has no significant association with viral load or CD4 cell count. The ratio of CD45RA(bright) to CD45RA(dim) CTL correlates significantly with CD4 cell count. This positive association decreases with antiretroviral treatment (ARV), indicating that suppression of viral replication alters the balance of circulating Gag-specific CD8(+) effector T cells. Subsets of cytolytic T cells may have distinct antiviral functions and further characterization of these effector CD8(+) T cells may yield important information on T cell regulation and dysfunction in HIV infection.
细胞毒性T淋巴细胞（CTL）在控制HIV感染中发挥着重要作用。最终无法控制HIV-1感染可能是由于HIV特异性CTL的功能受损。我们评估了HIV-1阳性乌干达人中针对Gag的细胞毒性。溶细胞活性标志物CD107在HIV感染个体的CD45RA（明亮型）和CD45RA（暗淡型）CD8(+) T细胞群体中均有表达。随着CD4细胞耗竭，针对Gag的CD107(+)CD45RA（明亮型）CD28(-)CCR7(-) CD8(+) T细胞的频率降低，且与Gag特异性辅助性T细胞反应的存在相关。相比之下，同一人群中针对Gag的CD107(+)CD45RA（暗淡型）CD28(-)CCR7(-) CD8(+) T细胞的频率与病毒载量或CD4细胞计数无显著关联。CD45RA（明亮型）与CD45RA（暗淡型）CTL的比例与CD4细胞计数显著相关。这种正相关在接受抗逆转录病毒治疗（ARV）后降低，表明病毒复制的抑制改变了循环中针对Gag的CD8(+)效应T细胞的平衡。细胞毒性T细胞亚群可能具有不同的抗病毒功能，对这些效应性CD8(+) T细胞的进一步表征可能会产生有关HIV感染中T细胞调节和功能障碍的重要信息。
