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. 1996 Apr;87(4):581–585. doi: 10.1046/j.1365-2567.1996.510589.x

HIV-1 upregulates Fas ligand expression in CD4+ T cells in vitro and in vivo: association with Fas-mediated apoptosis and modulation by aurintricarboxylic acid.

D Mitra 1, M Steiner 1, D H Lynch 1, L Staiano-Coico 1, J Laurence 1
PMCID: PMC1384136  PMID: 8675212

Abstract

CD4+ T-lymphocyte apoptosis has been associated with human immunodeficiency virus (HIV)-1 infection in vitro, paralleling the expression of Fas (APO-1, CD95) on peripheral blood mononuclear cells from patients with HIV disease. However, the link between Fas induction, T-cell activation, and cell death is unclear. We document, for the first time, marked upregulation of expression of mRNA for the ligand for Fas in peripheral blood mononuclear cells from HIV seropositive individuals, and demonstrate the ability of HIV infection to induce such expression in CD4+ T cells in vitro. We also define the relevance of this expression to HIV-mediated CD4+ T cell death. Our ability to downregulate Fas ligand message and suppress HIV-mediated apoptosis with aurintricarboxylic acid, a clinically used protease inhibitor with known activity against programmed cell death in other systems, may open up a new area of therapy for HIV infection.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alderson M. R., Tough T. W., Braddy S., Davis-Smith T., Roux E., Schooley K., Miller R. E., Lynch D. H. Regulation of apoptosis and T cell activation by Fas-specific mAb. Int Immunol. 1994 Nov;6(11):1799–1806. doi: 10.1093/intimm/6.11.1799. [DOI] [PubMed] [Google Scholar]
  2. Cheng J., Zhou T., Liu C., Shapiro J. P., Brauer M. J., Kiefer M. C., Barr P. J., Mountz J. D. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science. 1994 Mar 25;263(5154):1759–1762. doi: 10.1126/science.7510905. [DOI] [PubMed] [Google Scholar]
  3. Darzynkiewicz Z., Bruno S., Del Bino G., Gorczyca W., Hotz M. A., Lassota P., Traganos F. Features of apoptotic cells measured by flow cytometry. Cytometry. 1992;13(8):795–808. doi: 10.1002/cyto.990130802. [DOI] [PubMed] [Google Scholar]
  4. Debatin K. M., Fahrig-Faissner A., Enenkel-Stoodt S., Kreuz W., Benner A., Krammer P. H. High expression of APO-1 (CD95) on T lymphocytes from human immunodeficiency virus-1-infected children. Blood. 1994 May 15;83(10):3101–3103. [PubMed] [Google Scholar]
  5. Gougeon M. L., Garcia S., Heeney J., Tschopp R., Lecoeur H., Guetard D., Rame V., Dauguet C., Montagnier L. Programmed cell death in AIDS-related HIV and SIV infections. AIDS Res Hum Retroviruses. 1993 Jun;9(6):553–563. doi: 10.1089/aid.1993.9.553. [DOI] [PubMed] [Google Scholar]
  6. Henkart P. A. Apoptosis: O death, where is thy sting? J Immunol. 1995 May 15;154(10):4905–4908. [PubMed] [Google Scholar]
  7. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  8. Jacobson M. D., Burne J. F., Raff M. C. Programmed cell death and Bcl-2 protection in the absence of a nucleus. EMBO J. 1994 Apr 15;13(8):1899–1910. doi: 10.1002/j.1460-2075.1994.tb06459.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Katsikis P. D., Wunderlich E. S., Smith C. A., Herzenberg L. A., Herzenberg L. A. Fas antigen stimulation induces marked apoptosis of T lymphocytes in human immunodeficiency virus-infected individuals. J Exp Med. 1995 Jun 1;181(6):2029–2036. doi: 10.1084/jem.181.6.2029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kawasaki T., Kaku S., Kohinata T., Sakai Y., Taniuchi Y., Kawamura K., Yano S., Takenaka T., Fujimura Y. Inhibition by aurintricarboxylic acid of von Willebrand factor binding to platelet GPIb, platelet retention, and thrombus formation in vivo. Am J Hematol. 1994 Sep;47(1):6–15. doi: 10.1002/ajh.2830470103. [DOI] [PubMed] [Google Scholar]
  11. Kobayashi N., Hamamoto Y., Yamamoto N., Ishii A., Yonehara M., Yonehara S. Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9620–9624. doi: 10.1073/pnas.87.24.9620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Laurence J., Cooke H., Sikder S. K. Effect of tamoxifen on regulation of viral replication and human immunodeficiency virus (HIV) long terminal repeat-directed transcription in cells chronically infected with HIV-1. Blood. 1990 Feb 1;75(3):696–703. [PubMed] [Google Scholar]
  13. Laurence J., Hodtsev A. S., Posnett D. N. Superantigen implicated in dependence of HIV-1 replication in T cells on TCR V beta expression. Nature. 1992 Jul 16;358(6383):255–259. doi: 10.1038/358255a0. [DOI] [PubMed] [Google Scholar]
  14. Laurence J., Mitra D., Steiner M., Lynch D. H., Siegal F. P., Staiano-Coico L. Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia. J Clin Invest. 1996 Feb 1;97(3):672–680. doi: 10.1172/JCI118464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Muller S., Richalet P., Laurent-Crawford A., Barakat S., Rivière Y., Porrot F., Chamaret S., Briand J. P., Montagnier L., Hovanessian A. Autoantibodies typical of non-organ-specific autoimmune diseases in HIV-seropositive patients. AIDS. 1992 Sep;6(9):933–942. doi: 10.1097/00002030-199209000-00004. [DOI] [PubMed] [Google Scholar]
  16. Muro-Cacho C. A., Pantaleo G., Fauci A. S. Analysis of apoptosis in lymph nodes of HIV-infected persons. Intensity of apoptosis correlates with the general state of activation of the lymphoid tissue and not with stage of disease or viral burden. J Immunol. 1995 May 15;154(10):5555–5566. [PubMed] [Google Scholar]
  17. Nicholson D. W., Ali A., Thornberry N. A., Vaillancourt J. P., Ding C. K., Gallant M., Gareau Y., Griffin P. R., Labelle M., Lazebnik Y. A. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995 Jul 6;376(6535):37–43. doi: 10.1038/376037a0. [DOI] [PubMed] [Google Scholar]
  18. Oyaizu N., McCloskey T. W., Coronesi M., Chirmule N., Kalyanaraman V. S., Pahwa S. Accelerated apoptosis in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus type-1 infected patients and in CD4 cross-linked PBMCs from normal individuals. Blood. 1993 Dec 1;82(11):3392–3400. [PubMed] [Google Scholar]
  19. Razvi E. S., Welsh R. M. Apoptosis in viral infections. Adv Virus Res. 1995;45:1–60. doi: 10.1016/s0065-3527(08)60057-3. [DOI] [PubMed] [Google Scholar]
  20. Silvestris F., Cafforio P., Frassanito M. A., Tucci M., Romito A., Nagata S., Dammacco F. Overexpression of Fas antigen on T cells in advanced HIV-1 infection: differential ligation constantly induces apoptosis. AIDS. 1996 Feb;10(2):131–141. doi: 10.1097/00002030-199602000-00002. [DOI] [PubMed] [Google Scholar]
  21. Takahashi T., Tanaka M., Inazawa J., Abe T., Suda T., Nagata S. Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol. 1994 Oct;6(10):1567–1574. doi: 10.1093/intimm/6.10.1567. [DOI] [PubMed] [Google Scholar]
  22. Terai C., Kornbluth R. S., Pauza C. D., Richman D. D., Carson D. A. Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. J Clin Invest. 1991 May;87(5):1710–1715. doi: 10.1172/JCI115188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Westendorp M. O., Frank R., Ochsenbauer C., Stricker K., Dhein J., Walczak H., Debatin K. M., Krammer P. H. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature. 1995 Jun 8;375(6531):497–500. doi: 10.1038/375497a0. [DOI] [PubMed] [Google Scholar]
  24. Yang Y., Merćep M., Ware C. F., Ashwell J. D. Fas and activation-induced Fas ligand mediate apoptosis of T cell hybridomas: inhibition of Fas ligand expression by retinoic acid and glucocorticoids. J Exp Med. 1995 May 1;181(5):1673–1682. doi: 10.1084/jem.181.5.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]

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