Differential replication of human immunodeficiency virus type 1 in CD8- and CD8+ subsets of natural killer cells: relationship to cytokine production pattern.
CD8+ and CD8- subsets of peripheral blood natural killer (NK) cells were examined for susceptibility to infection with human immunodeficiency virus type 1 (HIV-1) and for the ability to produce various types of interferon (IFN) and tumor necrosis factor (TNF). HIV-1 was preferentially grown in CD8+ NK cells. The ability of CD8- NK cells to suppress HIV-1 replication was related to their ability to produce alpha IFN (IFN-alpha) upon viral induction. Induction with interleukin-2 resulted in IFN-gamma production in both subsets of NK cells. In the CD8+ subset, IFN-gamma and HIV-1 mutually enhanced the production of TNF alpha, leading to hyperactivation of viral replication, whereas in CD8- NK cells IFN-gamma primed HIV-induced IFN-alpha production. The dichotomous effects of IFN-gamma on HIV-1 replication were dependent on the IFN-alpha-producing ability of the cellular targets. These findings can explain the selective depletion of the CD16+ CD8+ subset that begins early in the in vivo HIV-1 infection.
Danish Cancer Society, Department of Virus and Cancer, Aarhus.
F D
FD
Tóth
P
P
Mosborg-Petersen
J
J
Kiss
G
G
Aboagye-Mathiesen
M
M
Zdravkovic
H
H
Hager
P
P
Ebbesen
D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D007700:Kinetics; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D015703:Antigens, CD; D016827:CD8 Antigens; D016898:Interferon-alpha; D007376:Interleukin-2; D007371:Interferon-gamma