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HIV-1 envelope glycoprotein gp120 down-regulates CD4 expression in primary human macrophages through induction of endogenous tumour necrosis factor-alpha.

Abstract：

: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-alpha (TNF-alpha) 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-alpha monoclonal antibody (mAb), but not by mAb directed against other cytokines induced by rgp120, such as interleukin-1 beta (IL-1 beta) and interferon-alpha (IFN-alpha). 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-alpha 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.

journal_name

Immunology

journal_title

Immunology

authors

Karsten V,Gordon S,Kirn A,Herbein G

doi

10.1046/j.1365-2567.1996.d01-648.x

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

55-60

issue

eissn

0019-2805

issn

1365-2567

journal_volume

pub_type

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HIV-1 envelope glycoprotein gp120 down-regulates CD4 expression in primary human macrophages through induction of endogenous tumour necrosis factor-alpha.