Document 0252 DOCN M9460252 TI HIV-1 gp120 and anti-gp120 induce reversible unresponsiveness in peripheral CD4 T lymphocytes. DT 9404 AU Liegler TJ; Stites DP; Department of Laboratory Medicine, University of California, San; Francisco. SO J Acquir Immune Defic Syndr. 1994 Apr;7(4):340-8. Unique Identifier : AIDSLINE MED/94180307 AB 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. DE Antibodies, Monoclonal/*IMMUNOLOGY Antigens, CD4/IMMUNOLOGY Cell Survival Dose-Response Relationship, Immunologic Human HIV Antibodies/IMMUNOLOGY HIV Envelope Protein gp120/*IMMUNOLOGY *HIV Seronegativity HIV-1/*IMMUNOLOGY Interleukin-2/IMMUNOLOGY Leukocytes, Mononuclear/IMMUNOLOGY Lymphocyte Subsets/IMMUNOLOGY Lymphocyte Transformation Receptors, Antigen, T-Cell/IMMUNOLOGY Recombinant Proteins/IMMUNOLOGY Support, U.S. Gov't, P.H.S. T4 Lymphocytes/*IMMUNOLOGY JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).