Spontaneous and anti-Fas-induced apoptosis in lymphocytes from HIV-infected patients undergoing highly active anti-retroviral therapy.
OBJECTIVE
The aim of this study was to investigate susceptibility to spontaneous or anti-Fas-induced apoptosis in peripheral blood mononuclear cells (PBMC) from HIV-positive patients before and during highly active anti-retroviral therapy (HAART).


METHODS
A longitudinal study was performed on 12 evaluable patients on HAART. This cohort was analysed prior to and at week 2, 4, 8, 16 and 24 after beginning HAART. Variations in CD4 and CD8 cells, viral load, susceptibility to spontaneous or anti-Fas-induced apoptosis in the presence of IL-2, IL-4 or IL-12 were studied. Expression of Fas and Bcl-2 were also assessed.


METHODS
Levels of HIV RNA were determined by a quantitative reverse transcription-PCR assay. Apoptosis was evaluated by staining isolated nuclei with propidium iodide followed by multiparameter flow cytometry analysis.


RESULTS
Spontaneous apoptosis of PBMC was promptly inhibited after the start of treatment. Similarly, anti-Fas-induced apoptosis diminished greatly during treatment. Expression of Fas decreased significantly, while that of Bcl-2 remained statistically unchanged during the first 24 weeks of therapy. Levels of apoptosis correlated inversely to CD4 cell counts and directly to viral load in a highly significant way. Expression of Fas was directly correlated to apoptosis. Interleukin (IL)-2, but not IL-4 or IL-12, protected PBMC of HIV-positive individuals from spontaneous or anti-Fas-induced apoptosis before and during HAART.


CONCLUSIONS
These results suggest that regulation of apoptosis and of Fas expression are involved in immunoreconstitution during HAART.
Grelli
S
S
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Campagna
S
S
Lichtner
M
M
Ricci
G
G
Vella
S
S
Vullo
V
V
Montella
F
F
Di Fabio
S
S
Favalli
C
C
Mastino
A
A
Macchi
B
B
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000494:pharmacology; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D019562:Viral Load; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
D019380:Anti-HIV Agents; D007378:Interleukins; D019253:Proto-Oncogene Proteins c-bcl-2; D018894:Reverse Transcriptase Inhibitors; D019014:fas Receptor