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AIDS patient monocytes target CD4 T cells for cellular conjugate formation and deletion through the membrane expression of HIV-1 envelope molecules.

Abstract
The human immunodeficiency virus (HIV) causes in humans the acquired immunodeficiency syndrome (AIDS). It replicates at a high rate in lymphoid organs even before it causes clinical symptoms. It binds to CD4 cell surface markers and destroys T lymphocytes that express the receptor. The immune system replenishes CD4 T cells at a formidable rate but, unable to keep up with the losses, allows the CD4 T cell compartment to disintegrate gradually. The net loss of CD4 T cells is an indicator for disease progression. How the virus destroys CD4 T cells and whether their loss accounts for the ensuing immunodeficiency have not been fully explained. We have reported evidence, and confirm here, that HIV-infected subjects deposit on monocytes immune complexes containing the virus or its envelope molecule gp120. Armed with these immune complexes monocytes form specific cellular conjugates with CD4 T cells and kill them. The destruction of normal CD4 T cells by monocytes from AIDS patients can be blocked by soluble CD4 and by free gp120. Normal monocytes and macrophages can be armed with CD4-binding gp120, and so induced to destroy CD4 T cells, by incubating them with gp120 and gp120-specific antibody. CD4-reactive HIV-1 components have a short half-life on the phagocyte surface. Removed from the HIV-infected environment, monocytes clear their surfaces of antibody-complexed viral components within hours, which abrogates their ability to destroy CD4 T cells. Rearming the monocytes with gp120-anti-gp120 complexes restores their capacity to destroy CD4 T cells. The data imply that for uninterrupted deletion of CD4 T cells, monocytes require a continued productive HIV-1 infection of their host.
AuthorsA Dudhane, Z Q Wang, T Orlikowsky, A Gupta, G P Wormser, H Horowitz, P Kufer, M K Hoffmann
JournalAIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 12 Issue 10 Pg. 893-9 (Jul 01 1996) ISSN: 0889-2229 [Print] United States
PMID8798974 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigen-Antibody Complex
  • CD4 Antigens
  • HIV Envelope Protein gp120
Topics
  • Acquired Immunodeficiency Syndrome (blood, immunology)
  • Adult
  • Antigen-Antibody Complex (immunology)
  • CD4 Antigens (immunology)
  • CD4-Positive T-Lymphocytes (immunology)
  • Clonal Deletion
  • HIV Envelope Protein gp120 (immunology)
  • Humans
  • Monocytes (immunology)

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