Inhibition of Antigen-Induced Lymphocyte Proliferation by Tat Protein from HIV-1

• Published in: Science (American Association for the Advancement of Science) 1989-12, Vol.246 (4937), p.1606-1608
• Main Authors: Viscidi, Raphael P., Mayur, Kumudini, Lederman, Howard M., Frankel, Alan D.
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - immunology; AIDS; AIDS/HIV; Amino acids; Biological and medical sciences; Cells, Cultured; Concanavalin A; COS cells; Cultured cells; DNA Replication - drug effects; Fundamental and applied biological sciences. Psychology; Gene Products, tat - immunology; Gene Products, tat - pharmacology; HeLa cells; HeLa Cells - metabolism; HIV; HIV (Viruses); HIV 1; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Immunosuppression; Lymphocyte Activation - drug effects; Lymphocyte proliferation; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - immunology; Medical research; Microbiology; Natural killer cells; Pokeweed Mitogens; Promoter Regions, Genetic; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Reproduction; Staphylococcal Protein A; T lymphocytes; tat Gene Products, Human Immunodeficiency Virus; Tetanus; Tetanus toxoid; Trans-Activators - pharmacology; Transcriptional Activation; Virology; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2556795

The purified human immunodeficiency virus type-1 (HIV-1) 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.