Impairment of T cell receptor-dependent stimulation in CD4+ lymphocytes after contact with membrane-bound HIV-1 envelope glycoprotein.
A CD4+ human T cell clone (SPB21) or primary blood mononuclear cells were grown in the presence of HeLa cells stably expressing functional human immunodeficiency virus type 1 envelope glycoprotein complexes at their surface. After a short cocultivation, SPB21 cells lost their ability to proliferate in response to T cell receptor (TCR) stimulations and died by apoptosis, whereas interleukin-2 stimulation was still effective. Incubation with soluble monomeric gp120 did not alter TCR responsiveness. A selective decrease in the proportion of CD4+ cells was also observed among primary lymphocytes after cocultivation and OKT3 stimulation. We propose that binding of oligomeric membrane-bound envelope glycoprotein induces a multimerization of CD4 molecules that impairs normal TCR stimulation.
Schwartz
O
O
Département SIDA et Rétrovirus, Institut Pasteur, Paris, France.
Alizon
M
M
Heard
J M
JM
Danos
O
O
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002999:Clone Cells; D015686:Gene Products, env / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D008213:Lymphocyte Activation; D011498:Protein Precursors / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins