Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway.
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.
Ott
M
M
The Picower Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
Emiliani
S
S
Van Lint
C
C
Herbein
G
G
Lovett
J
J
Chirmule
N
N
McCloskey
T
T
Pahwa
S
S
Verdin
E
E
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
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