Center for AIDS Research, Duke University Medical Center, Durham, NC 22710, USA.
J Immunol. 2012 May 1;188(9):4289-96. doi: 10.4049/jimmunol.1103701. Epub 2012 Mar 28.
Previous studies have revealed that HIV-infected individuals possess circulating CD4(+)CD8(+) double-positive (DP) T cells specific for HIV Ags. In the present study, we analyzed the proliferation and functional profile of circulating DP T cells from 30 acutely HIV-infected individuals and 10 chronically HIV-infected viral controllers. The acutely infected group had DP T cells that showed more proliferative capability and multifunctionality than did both their CD4(+) and CD8(+) T cells. DP T cells were found to exhibit greater proliferation and higher multifunctionality compared with CD4 T cells in the viral controller group. The DP T cell response represented 16% of the total anti-HIV proliferative response and >70% of the anti-HIV multifunctional response in the acutely infected subjects. Proliferating DP T cells of the acutely infected subjects responded to all HIV Ag pools with equal magnitude. Conversely, the multifunctional response was focused on the pool representing Nef, Rev, Tat, VPR, and VPU. Meanwhile, the controllers' DP T cells focused on Gag and the Nef, Rev, Tat, VPR, and VPU pool for both their proliferative and multifunctional responses. Finally, we show that the presence of proliferating DP T cells following all HIV Ag stimulations is well correlated with proliferating CD4 T cells whereas multifunctionality appears to be largely independent of multifunctionality in other T cell compartments. Therefore, DP T cells represent a highly reactive cell population during acute HIV infection, which responds independently from the traditional T cell compartments.
先前的研究表明，HIV 感染者体内存在针对 HIV 抗原的循环 CD4+CD8+双阳性（DP）T 细胞。在本研究中，我们分析了 30 名急性 HIV 感染者和 10 名慢性 HIV 感染者中的病毒控制者的循环 DP T 细胞的增殖和功能特征。与 CD4+和 CD8+T 细胞相比，急性感染组的 DP T 细胞显示出更强的增殖能力和多功能性。与病毒控制组的 CD4 T 细胞相比，DP T 细胞表现出更强的增殖能力和更高的多功能性。DP T 细胞反应代表了急性感染患者总抗 HIV 增殖反应的 16%和抗 HIV 多功能反应的 >70%。急性感染患者的增殖 DP T 细胞对所有 HIV Ag 池的反应强度相等。相反，多功能反应集中在代表 Nef、Rev、Tat、VPR 和 VPU 的池上。同时，控制者的 DP T 细胞对 Gag 和 Nef、Rev、Tat、VPR 和 VPU 池的增殖和多功能反应均有反应。最后，我们表明，在所有 HIV Ag 刺激后存在增殖的 DP T 细胞与增殖的 CD4 T 细胞密切相关，而多功能性似乎在很大程度上独立于其他 T 细胞区室的多功能性。因此，DP T 细胞代表急性 HIV 感染期间高度反应性的细胞群体，其反应独立于传统的 T 细胞区室。
