In vitro replication of HIV-1 in naturally infected CD4+ T cells is inhibited by rIFN alpha 2 and by a soluble factor secreted by activated CD8+ T cells, but not by rIFN beta, rIFN gamma, or recombinant tumor necrosis factor-alpha.
The effect of lymphokines on the replication of HIV-1 has previously been investigated using HIV-1-infected cell lines or PBMCs infected in vitro with HIV-1. We have examined the effect of rIFN alpha 2, rFIN beta, and rIFN gamma and recombinant tumor necrosis factor-alpha (rTNF alpha) on the replication of HIV-1 in vitro in naturally HIV-1-infected CD4+ T cells from asymptomatic HIV-1-seropositive individuals. rIFN alpha 2 inhibited the replication of HIV-1 effectively at concentrations that can be achieved in vivo. The inhibitory activity was most efficacious when rIFN alpha 2 was added as the CD4+ T cells were being activated, and less but still considerable when rIFN alpha 2 was added 4-96 h after CD4+ T-cell activation. rIFN alpha 2 exerted a suppressive effect on the proliferation of the CD4+ T cells, but this effect was small at concentrations that caused 90% inhibition of the replication of HIV-1. rIFN beta, rIFN gamma, and rTNF alpha had no effect on the replication of HIV-1, but rIFN beta and rTNF alpha had a costimulatory effect on CD4+ T-cell proliferation. Activated CD8+ T cells secrete a HIV-1-inhibitory soluble factor. Blocking experiments using an IFN alpha 2-neutralizing MAb showed that this HIV-1-inhibitory factor is not IFN alpha 2.
Brinchmann
J E
JE
Institute of Transplantation Immunology, National Hospital, Oslo, Norway.
Gaudernack
G
G
Vartdal
F
F
D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000382:microbiology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D011994:Recombinant Proteins; D012995:Solubility; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma