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 an important role in inducing functional suppression and depletion of CD4 lymphocytes following infection with HIV. In order to further understand the mechanisms involved in HIV-induced immunosuppression, we have studied the effects of recombinant HIV-1 gp120/SF2 and anti-gp120/SF2 antibodies on T cell receptor (TCR)-mediated proliferation of peripheral blood mononuclear cells (PBMCs) and isolated lymphocyte subsets from HIV-seronegative donors. In a dose-dependent manner, gp120 significantly reduces the proliferative responses of unfractionated PBMCs and highly enriched CD4 T lymphocytes when they are polyclonally stimulated through the TCR using WT31 (anti-alpha beta Ti chains) and anti-Leu 4 (anti-CD3 epsilon) in the presence of autologous accessory cells. The addition of divalent anti-gp120/SF2 to lymphocytes previously incubated with gp120 further reduces the proliferation to the levels seen after pretreating cells with divalent anti-CD4 (anti-Leu 3a). CD8 T lymphocytes, on the other hand, show no change in TCR-mediated proliferation following preincubation with either anti-CD4 or gp120/anti-gp120. We find no evidence for significant cell death by apoptosis using methods 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 induction of reversible functional anergy.
Liegler
T J
TJ
Department of Laboratory Medicine, University of California, San Francisco.
Stites
D P
DP
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D004306:Dose-Response Relationship, Immunologic; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D018023:HIV Seronegativity; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins