Culturing of human peripheral blood cells reveals unsuspected lymphocyte responses relevant to HIV disease.
Recombinant HIV-Tat (Tat) induces extensive apoptosis in peripheral blood mononuclear cells (PBMCs) cultured in typical CO2 incubators, which are equilibrated with air (21% O2). However, as we show here, Tat apoptosis induction fails in PBMCs cultured at physiological oxygen levels (5% O2). Under these conditions, Tat induces PBMCs to divide, efficiently primes them for HIV infection, and supports virus production by the infected cells. Furthermore, Tat takes only 2 h to prime PBMCs under these conditions. In contrast, PHA/IL-2, which is widely used to prime cells for HIV infection, takes 2-3 days. These findings strongly recommend culturing primary cells at physiological oxygen levels. In addition, they suggest HIV-Tat as a key regulator of HIV disease progression.
Sahaf
Bita
B
Department of Genetics and Department of Pediatrics, Division of Stem Cell Transplantation, Stanford University School of Medicine, Stanford, CA 94305, USA.
Atkuri
Kondala
K
Heydari
Kartoosh
K
Malipatlolla
Meena
M
Rappaport
Jay
J
Regulier
Emmanuel
E
Herzenberg
Leonard A
LA
Herzenberg
Leonore A
LA
D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division / Q000187:drug effects; D018450:Disease Progression; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D015696:Gene Products, tat; D007376:Interleukin-2; D010100:Oxygen