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

被引:18
|
作者
Dudhane, A
Wang, ZQ
Orlikowsky, T
Gupta, A
Wormser, GP
Horowitz, H
Kufer, P
Hoffmann, MK
机构
[1] NEW YORK MED COLL, DEPT MICROBIOL & IMMUNOL, VALHALLA, NY 10595 USA
[2] NEW YORK MED COLL, DEPT PEDIAT, VALHALLA, NY 10595 USA
[3] NEW YORK MED COLL, DEPT INFECT DIS, VALHALLA, NY 10595 USA
[4] UNIV MUNICH, INST IMMUNOL, W-8000 MUNICH, GERMANY
关键词
D O I
10.1089/aid.1996.12.893
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 tbe 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.
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页码:893 / 899
页数:7
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