The activation and dynamics of cytokine expression by CD4+ T cells and AIDS progression in HIV-1-infected Chinese individuals

Abstract: 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. [Copyright &y& Elsevier]