Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1.
The purified human immunodeficiency virus type-l (HIV-l) Tat protein inhibited lymphocyte proliferation induced by tetanus toxoid or Candida antigens by 66 to 97% at nanomolar concentrations of Tat. In contrast, Tat did not cause a significant reduction of lymphocyte proliferation in response to mitogens such as phytohemagglutinin or pokeweed mitogen. Inhibition was blocked by oxidation of the cysteine-rich region of Tat or by incubation with an antibody to Tat before the assay. A synthetic Tat peptide (residues 1 to 58) also inhibited antigen-stimulated proliferation. Experiments with H9 and U937 cell lines showed that Tat can easily enter both lymphocytes and monocytes. The specific inhibition of antigen-induced lymphocyte proliferation by Tat mimics the effect seen with lymphocytes from HIV-infected individuals and suggests that Tat might directly contribute to the immunosuppression associated with HIV infection.
Viscidi
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RP
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Mayur
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Lederman
H M
HM
Frankel
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AD
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A; D004261:DNA Replication / Q000187:drug effects; D015696:Gene Products, tat / Q000276:immunology / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D011043:Pokeweed Mitogens; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D013205:Staphylococcal Protein A; D015534:Trans-Activators / Q000494:pharmacology*; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D011043:Pokeweed Mitogens; D011994:Recombinant Proteins; D013205:Staphylococcal Protein A; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus; D003208:Concanavalin A