Early T-cell apoptosis and Fas expression during antiretroviral therapy in individuals infected with human immunodeficiency virus-1.
Several lines of evidence suggest that Fas-mediated apoptosis is involved in the CD4 T-cell depletion in human immunodeficiency virus-1 (HIV-1) infection. To investigate this, we studied changes in peripheral blood, early T-cell apoptosis and Fas expression after initiation of antiretroviral therapy (ART) in 18 HIV-1-infected individuals. Flow cytometric analysis was performed with Apostain and CD4, CD8 and Fas staining. Fas expression was quantified by standardized beads. The levels of CD4 and CD8 T cells with early apoptosis were increased comparably in HIV-1-infected individuals. Despite elevated CD4 T cell counts, no decline in early T-cell apoptosis could be detected during the first 8 weeks of ART. However, after 26 weeks of ART in five patients that showed a sustained reduction of viral replication there was a marked decrease in T cells with features of early apoptosis. No difference was found for Fas expression on early apoptotic T cells. Fas expression on CD4 and CD8 T cells was reduced after initiation of ART; this was independent of the CD4 T-cell trend and indicates that the immediate CD4 T-cell expansion during ART is probably not the result of a decreased rate of early apoptosis among peripheral blood CD4 T cells. However, preliminary data imply a long-term reduction of early T-cell apoptosis and Fas expression in patients who show a sustained reduction of viral replication.
Department of Medicine II, Medical University Lübeck, Germany.
S P
SP
Aries
K
K
Weyrich
B
B
Schaaf
F
F
Hansen
R H
RH
Dennin
K
K
Dalhoff
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D019562:Viral Load; D019014:fas Receptor / Q000096:biosynthesis*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019014:fas Receptor