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PMID: 2315327 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 6 ·1990-03-00 ·Pages 2379-83

Oyaizu N, Chirmule N, Kalyanaraman VS, Hall WW, Pahwa R, Shuster M, Pahwa S

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) alpha-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.

MeSH Terms
Antigens, CD/immunology Blotting, Northern CD4 Antigens/immunology Cell Membrane/immunology Cells, Cultured Clone Cells HIV Envelope Protein gp120/immunology HIV-1/immunology Humans Interleukin-2/genetics Lymphocyte Activation RNA, Messenger/antagonists & inhibitors,genetics T-Lymphocytes/immunology
Chemicals
Antigens, CD CD4 Antigens HIV Envelope Protein gp120 Interleukin-2 RNA, Messenger
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Oyaizu N
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030.
Chirmule N
Kalyanaraman V S
Hall W W
Pahwa R
Shuster M
Pahwa S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.6.2379
Published
1990-03-00
Pages
2379-83
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC53690
Subset
IM
Grants
NIAID NIH HHS · AI 28281 · United States
NCI NIH HHS · CA40931 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1073/pnas.87.6.2379 PMC Full Text View journal details
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