Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA

N. Oyaizu, N. Chirmule, V. S. Kalyanaraman, W. W. Hall, R. A. Good, S. Pahwa

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

Envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1) is known to inhibit T-cell function, but little is known about the mechanisms of this immunosuppression. Pretreatment of a CD4+ tetanus toxoid-specific T-cell clone with soluble gp120 was found to exert a dose-dependent inhibition of soluble antigen-driven or anti-CD3 monoclonal antibody-driven proliferative response, interleukin 2 (IL-2) production, and surface IL-2 receptor (IL-2R) α-chain expression, all of which were reversed by the addition of exogenous IL-2. mRNA for the gene encoding IL-2 was suppressed by treatment with gp120, but IL-2R gene transcription was not inhibited. Bypass activation of the T-cell clone with phorbol 12-myristate 13-acetate plus ionomycin was unaffected by gp120 pretreatment. Thus, gp120-CD4 interaction interferes with an essential role of the CD4 molecule in signal transduction through the CD3-antigen receptor (Ti) complex. Such a mechanism of gp120-induced immunosuppression, if operative in vivo, could contribute to the depressed specific immune responses associated with HIV infection.

Original languageEnglish (US)
Pages (from-to)2379-2383
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number6
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

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Keywords

  • CD4 molecule
  • Interleukin 2 receptor α chain
  • T-cell activation

ASJC Scopus subject areas

  • Genetics
  • General

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