Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, PR China.
Microb Pathog. 2012 Nov-Dec;53(5-6):189-97. doi: 10.1016/j.micpath.2012.07.008. Epub 2012 Aug 11.
CD4(+) T cells are the main targets of HIV-1 and play a central role during the progression of AIDS, but the mechanism has not been clearly elucidated. In the present study, blood samples were collected from HIV-1-infected Chinese individuals, including typical progressors (TPs) and long-term nonprogressors (LTNPs). More HIV-1 productively infected CD4(+) T cells were obtained through co-cultures and the infected CD4(+) T cells were discriminated from bystander cells by intracellular p24 staining. The activation level and dynamics of cytokine expression of CD4(+) T cells were analyzed. After stimulating the freshly isolated PBMCs with PHA, the frequencies of CD69(+)CD4(+) T cells/CD25(+)CD4(+) T cells were higher in TP than in LTNP group and were positively correlated with viral load and negatively correlated with CD4(+) T cell counts. The activation level of CD4(+) T cells in the co-cultured PBMCs was higher in TP than in LTNP group, and HIV-1 productively infected CD4(+) T cells were more activated than bystander CD4(+) T cells. The expression of Th1 cytokines (IL-2 and IFN-γ) and the frequency of Th1 cells in co-cultured PBMCs were lower in TP than in LTNP group. HIV-1 productively infected CD4(+) T cells expressed higher level of Th1/Th2 cytokines than bystander cells. More productive HIV-1 infection occurred in Th1 than in Th2 cells, followed by Th0 cells. The present results suggest that the excessive activation level of CD4(+) T cells and the preferential replication of HIV-1 in Th1 cells that lead to the shift of Th1 to Th2 are likely crucial to AIDS progression in HIV-1-infected Chinese individuals.
CD4(+) T 细胞是 HIV-1 的主要靶标，在艾滋病的进展过程中发挥着核心作用，但机制尚未明确。本研究采集了 HIV-1 感染的中国个体的血液样本，包括典型进展者（TPs）和长期非进展者（LTNPs）。通过共培养获得更多的 HIV-1 有效感染的 CD4(+) T 细胞，并通过细胞内 p24 染色将感染的 CD4(+) T 细胞与旁观者细胞区分开来。分析 CD4(+) T 细胞的激活水平和细胞因子表达的动力学。用 PHA 刺激新鲜分离的 PBMC 后，TP 组中 CD69(+)CD4(+) T 细胞/CD25(+)CD4(+) T 细胞的频率高于 LTNP 组，且与病毒载量呈正相关，与 CD4(+) T 细胞计数呈负相关。共培养 PBMC 中 CD4(+) T 细胞的激活水平在 TP 组中高于 LTNP 组，且 HIV-1 有效感染的 CD4(+) T 细胞比旁观者 CD4(+) T 细胞更活跃。共培养 PBMC 中 Th1 细胞因子（IL-2 和 IFN-γ）的表达和 Th1 细胞的频率在 TP 组中低于 LTNP 组。HIV-1 有效感染的 CD4(+) T 细胞表达更高水平的 Th1/Th2 细胞因子，高于旁观者细胞。Th1 细胞比 Th2 细胞更容易发生 HIV-1 的有效感染，其次是 Th0 细胞。这些结果表明，CD4(+) T 细胞的过度激活水平和 HIV-1 优先在 Th1 细胞中复制，导致 Th1 向 Th2 的转变，可能是 HIV-1 感染的中国个体 AIDS 进展的关键因素。
