title: Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway.
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.
authors.affiliation: The Picower Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ott
authors.forename: S
authors.initials: S
authors.lastname: Emiliani
authors.forename: C
authors.initials: C
authors.lastname: Van Lint
authors.forename: G
authors.initials: G
authors.lastname: Herbein
authors.forename: J
authors.initials: J
authors.lastname: Lovett
authors.forename: N
authors.initials: N
authors.lastname: Chirmule
authors.forename: T
authors.initials: T
authors.lastname: McCloskey
authors.forename: S
authors.initials: S
authors.lastname: Pahwa
authors.forename: E
authors.initials: E
authors.lastname: Verdin
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D005091:Exons; D015696:Gene Products, tat / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000821:virology; D008213:Lymphocyte Activation; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D015215:Zidovudine / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D015696:Gene Products, tat; D007376:Interleukin-2; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D015215:Zidovudine