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.