AIDS patient monocytes target CD4 T cells for cellular conjugate formation and deletion through the membrane expression of HIV-1 envelope molecules.
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.
Dudhane
A
A
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595, USA.
Wang
Z Q
ZQ
Orlikowsky
T
T
Gupta
A
A
Wormser
G P
GP
Horowitz
H
H
Kufer
P
P
Hoffmann
M K
MK
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D000328:Adult; D000936:Antigen-Antibody Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017637:Clonal Deletion; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000276:immunology*
D000936:Antigen-Antibody Complex; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120