HIV-1 GP120 AND ANTI-GP120 INDUCE REVERSIBLE UNRESPONSIVENESS IN PERIPHERAL CD4 T-LYMPHOCYTES

Human immunodeficiency virus type 1 (HIV-1) gp-120 potentially plays a n important role in inducing functional suppression and depletion of C D4 lymphocytes following infection with HIV. In order to further under stand the mechanisms involved in HIV-induced immunosuppression, we hav e studied the effects of recombinant HIV-1 gp120/SF2 and anti-gp120/SF 2 antibodies on T cell receptor (TCR)-mediated proliferation of periph eral blood mononuclear cells (PBMCs) and isolated lymphocyte subsets f rom HIV-seronegative donors. In a dose-dependent manner, gp120 signifi cantly reduces the proliferative responses of unfractionated PBMCs and highly enriched CD4 T lymphocytes when they are polyclonally stimulat ed through the TCR using WT31 (anti-alpha beta Ti chains) and anti-Leu 4 (anti-CD3 epsilon) in the presence of autologous accessory cells. T he addition of divalent anti-gp120/SF2 to lymphocytes previously incub ated with gp120 further reduces the proliferation to the levels seen a fter pretreating cells with divalent anti-CD4 (anti-Leu 3a). CD8 T lym phocytes, on the other hand, show no change in TCR-mediated proliferat ion following preincubation with either anti-CD4 or gp120/anti-gp120. We find no evidence for significant cell death by apoptosis using meth ods of DNA analysis or flow cytometry and DNA-specific dyes to account for the loss of CD4 lymphocyte proliferation. Interleukin-2 restores the proliferation suppressed by gp120/anti-gp120 suggesting the induct ion of reversible functional anergy.