CD4-independent inhibition of lymphocyte proliferation mediated by HIV-1 envelope glycoproteins.
The cytopathic effects of HIV-1 produced by direct infection of human T cells do not account for the disproportionate loss of CD4-positive lymphocytes during the course of HIV infection. Previous studies have demonstrated the inhibition of uninfected human T cell activation and proliferation by the HIV-1 envelope glycoproteins, presumably due to gp120-CD4 interactions. To examine the ability of HIV-1 to inhibit T cell proliferation in the absence of both direct infection and gp120-CD4 interactions, we tested the effect of HIV-1 on mouse T cell proliferation. Culture media containing HIV-1 released from infected cells inhibited T lymphocyte proliferation in response to interleukin-2 (IL-2). Studies to explore the mechanism of this inhibition suggested that the decrease in proliferation resulted from interactions between HIV-1 and the mouse cells, but did not involve IL-2/IL-2 receptor interactions. We used monoclonal antibodies to demonstrate that the HIV-1 envelope glycoproteins were required for the inhibition of murine T cell proliferation. Anti-gp120 antibodies completely restored proliferation, indicating that the surface protein gp120 was primarily required for the inhibition of proliferation. However, antibodies directed against the transmembrane protein of HIV-1 (gp41) also partially restored lymphocyte proliferation. The functional significance of the HIV-1 envelope protein epitopes recognized by the monoclonal antibodies is discussed.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D002478:Cells, Cultured; D000939:Epitopes / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D014759:Viral Envelope Proteins / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007376:Interleukin-2; D014759:Viral Envelope Proteins