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HIV‐1 envelope glycoprotein gp120 down‐regulates CD4 expression in primary human macrophages through induction of endogenous tumour necrosis factor‐α
Author(s) -
KARSTEN V.,
GORDON S.,
KIRN A.,
HERBEIN G.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.d01-648.x
Subject(s) - endogeny , glycoprotein , envelope (radar) , tumor necrosis factor alpha , immunology , biology , primary (astronomy) , cancer research , microbiology and biotechnology , endocrinology , physics , computer science , telecommunications , radar , astronomy
Among immunological abnormalities present in human immunodeficiency virus type 1 (HIV‐1)‐infected individuals are dysregulation of cytokine production and CD4 down‐regulation in both T‐helper cells and monocytes/macrophages. The HIV‐1 envelope glycoprotein 120 (gp120) has the ability to induce different cytokines in peripheral blood mononuclear cells and in monocytes/macrophages in vitro which in some instances have been reported to down‐regulate macrophage CD4 expression. This study provides evidence that HIV‐1 recombinant gp120 (rgp120) down‐regulates both surface and total CD4 expression in primary tissue culture‐differentiated macrophages (TCDM) at the level of transcription. The CD4 down‐regulation observed in TCDM occurred between 6 and 12 hr after rgp120 treatment preceded by a peak of endogenous tumour necrosis factor‐α (TNF‐α) observed at 3–6 hr post‐treatment. We demonstrate that the TCDM CD4 down‐regulation observed after rgp120 treatment was inhibited by the use of an anti‐huTNF‐α monoclonal antibody (mAb), but not by mAb directed against other cytokines induced by rgp120, such as interleukin‐1β (IL‐1β) and interferon‐α (IFN‐α). The present findings roughly parallel those observed both in the sera of patients and in the monocytes/macrophages isolated from HIV‐positive individuals, suggesting that gp120 by stimulating endogenous TNF‐α production could be a good candidate for the CD4 down‐regulation observed in the monocytes/macrophages of HIV‐1‐infected individuals. In contrast to CD4 down‐regulation in HIV‐infected lymphocytes, which results from a direct effect of viral genes on CD4 expression, soluble factors such as cytokines induced during HIV infection might explain the monocyte/macrophage CD4 dysregulation observed in acquired immune deficiency syndrome.