Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway

Science. 1997 Mar 7;275(5305):1481-5. doi: 10.1126/science.275.5305.1481.

Abstract

Human immunodeficiency virus-type 1 (HIV-1) infection is characterized by a chronic state of immune hyperactivation in patients. Infection of human peripheral blood lymphocytes with HIV-1 in vitro resulted in increased interleukin-2 (IL-2) secretion in response to T cell activation via the CD3 and CD28 receptors. Expression of the HIV-1 transactivator Tat recapitulated this phenotype and was associated with increased IL-2 secretion in response to costimulation with CD3 plus CD28. IL-2 superinduction by Tat occurred at the transcriptional level, was mediated by the CD28-responsive element in the IL-2 promoter, and was exclusively dependent on the 29 amino acids encoded by the second exon of Tat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Antibodies, Monoclonal / immunology
  • CD28 Antigens / immunology*
  • CD3 Complex / immunology
  • Exons
  • Gene Products, tat / genetics
  • Gene Products, tat / physiology*
  • HIV Infections / immunology
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism*
  • Jurkat Cells
  • Leukocytes, Mononuclear / virology
  • Lymphocyte Activation*
  • Promoter Regions, Genetic
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transfection
  • Zidovudine / pharmacology
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Anti-HIV Agents
  • Antibodies, Monoclonal
  • CD28 Antigens
  • CD3 Complex
  • Gene Products, tat
  • Interleukin-2
  • Transcription Factors
  • tat Gene Products, Human Immunodeficiency Virus
  • Zidovudine