Retinoic acid inhibition of ex vivo human immunodeficiency virus-associated apoptosis of peripheral blood cells.
T cells from human immunodeficiency virus (HIV)-infected individuals undergo spontaneous and activation-induced ex vivo apoptosis. Here we report that peripheral blood mononuclear cells (PBMCs) obtained from six HIV-infected individuals exhibited reduced ex vivo DNA fragmentation and cell death after ingestion of all-trans-retinoic acid (tRA). These effects were attenuated with continued daily RA administration, which correlated with a > 5-fold decrease in serum peak RA concentrations. Incubation of PBMCs from HIV+ individuals with tRA in vitro resulted in decreased DNA fragmentation in a subset of patients, especially those having < 500 CD4+ T cells per mm3. tRA also inhibited apoptosis of preactivated normal PBMCs induced to die by restimulation, which raises the possibility of a common mechanism between activation-induced apoptosis of activated normal PBMCs and apoptosis associated with HIV infection. Whether HIV-associated apoptosis of PBMCs, and its prevention by RA, has an impact on T-cell survival or the course of disease in patients infected with HIV will require further evaluation.
Yang
Y
Y
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Bailey
J
J
Vacchio
M S
MS
Yarchoan
R
R
Ashwell
J D
JD
D000284:Administration, Oral; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004249:DNA Damage; D006678:HIV / Q000472:pathogenicity / Q000502:physiology*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006679:HIV Seropositivity / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016853:Muromonab-CD3 / Q000494:pharmacology / Q000627:therapeutic use; D014212:Tretinoin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D016853:Muromonab-CD3; D014212:Tretinoin