Diminished spontaneous apoptosis in lymphocytes from human immunodeficiency virus-infected long-term nonprogressors.
The relationship between peripheral lymphocyte apoptosis and human immunodeficiency virus disease progression was studied in infected subgroups with distinct profiles of progression. Long-term nonprogressors (LTNP) and seronegative controls had levels of spontaneous apoptosis significantly lower than those for recent seroconverters who had CD4 cell counts similar to those of nonprogressors but with a high likelihood of disease progression. Lymphocytes from nonprogressors and seronegative controls also showed negligible spontaneous caspase-3 activity, a biochemical indicator for apoptosis, whereas early progressors exhibited substantial activity. In contrast, when activated with mitogens, the lymphocytes from both LTNP and progressors displayed indistinguishable levels of heightened apoptosis. Spontaneous apoptosis and plasma viremia levels correlated positively in progressors, but not in LTNP. These findings demonstrate that increased lymphocyte apoptosis is evident prior to CD4 T cell decline and that LTNP are relatively resistant to the factors that induce accentuated levels of spontaneous but not mitogen-induced cell death.
Liegler
T J
TJ
Gladstone Institute of Virology and Immunology, San Francisco, California 94141-9100, USA. Teri_Liegler@quickmail.ucsf.edu
Yonemoto
W
W
Elbeik
T
T
Vittinghoff
E
E
Buchbinder
S P
SP
Greene
W C
WC
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000473:pathology*; D013379:Substrate Specificity; D017741:Survivors; D013997:Time Factors; D019562:Viral Load; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D020730:Guanine Nucleotide Dissociation Inhibitors; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D019204:GTP-Binding Proteins