The activation and dynamics of cytokine expression by CD4+ T cells and AIDS progression in HIV-1-infected Chinese individuals.
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.
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, PR China.
Yan
Y
Li
Wenhua
W
Ling
Huifang
H
Xu
Ming
M
Wang
Changyou
C
Wu
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology*; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D044466:Asian People; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D037181:Lectins, C-Type / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019562:Viral Load; D055815:Young Adult; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C508017:IL2RA protein, human