Apoptosis and apoptosis-associated perturbations of peripheral blood lymphocytes during HIV infection: comparison between AIDS patients and asymptomatic long-term non-progressors.
This study was designed to compare the degree of lymphocyte apoptosis and Fas-Fas ligand (FasL) expression in AIDS patients and long-term non-progressors (LTNPs) and correlate these parameters with apoptosis-associated perturbations in lymphocyte function. LTNPs had a lower frequency of apoptotic CD4+ and CD8+ T cells compared with subjects with AIDS. This correlated with a lower frequency of cells expressing Fas and FasL. The frequency of selected lymphocyte populations exhibiting a disrupted mitochondrial transmembrane potential (DeltaPsim) and increased superoxide generation was lower in LTNPs than in patients with AIDS; these abnormalities were associated with lower levels of caspase-1 activation in LTNPs. The results indicate a significantly reduced level of apoptosis and apoptosis-associated parameters in LTNPs than in patients developing AIDS. Based on these findings, a crucial role for mitochondria can be predicted in the process of lymphocyte apoptosis during the evolution of AIDS.
Moretti
S
S
Department of Experimental Medicine, University of L'Aquila, L'Aquila, Comunità di San Patrignano and Department of Emergency Medicine, Ospedale San Camillo, Rome, Italy.
Marcellini
S
S
Boschini
A
A
Famularo
G
G
Santini
G
G
Alesse
E
E
Steinberg
S M
SM
Cifone
M G
MG
Kroemer
G
G
De Simone
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005260:Female; D020276:HIV Long-Term Survivors; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D019014:fas Receptor