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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Mar 28;92(7):3051–3055. doi: 10.1073/pnas.92.7.3051

Retinoic acid inhibition of ex vivo human immunodeficiency virus-associated apoptosis of peripheral blood cells.

Y Yang 1, J Bailey 1, M S Vacchio 1, R Yarchoan 1, J D Ashwell 1
PMCID: PMC42357  PMID: 7708773

Abstract

T cells from human immunodeficiency virus (HIV)-infected individuals undergo spontaneous and activation-induced ex vivo apoptosis. Here we report that peripheral blood mononuclear cells (PBMCs) obtained from six HIV-infected individuals exhibited reduced ex vivo DNA fragmentation and cell death after ingestion of all-trans-retinoic acid (tRA). These effects were attenuated with continued daily RA administration, which correlated with a > 5-fold decrease in serum peak RA concentrations. Incubation of PBMCs from HIV+ individuals with tRA in vitro resulted in decreased DNA fragmentation in a subset of patients, especially those having < 500 CD4+ T cells per mm3. tRA also inhibited apoptosis of preactivated normal PBMCs induced to die by restimulation, which raises the possibility of a common mechanism between activation-induced apoptosis of activated normal PBMCs and apoptosis associated with HIV infection. Whether HIV-associated apoptosis of PBMCs, and its prevention by RA, has an impact on T-cell survival or the course of disease in patients infected with HIV will require further evaluation.

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Selected References

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  1. Ameisen J. C. Programmed cell death and AIDS: from hypothesis to experiment. Immunol Today. 1992 Oct;13(10):388–391. doi: 10.1016/0167-5699(92)90086-M. [DOI] [PubMed] [Google Scholar]
  2. Banda N. K., Bernier J., Kurahara D. K., Kurrle R., Haigwood N., Sekaly R. P., Finkel T. H. Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. J Exp Med. 1992 Oct 1;176(4):1099–1106. doi: 10.1084/jem.176.4.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bishop S. A., Gruffydd-Jones T. J., Harbour D. A., Stokes C. R. Programmed cell death (apoptosis) as a mechanism of cell death in peripheral blood mononuclear cells from cats infected with feline immunodeficiency virus (FIV). Clin Exp Immunol. 1993 Jul;93(1):65–71. doi: 10.1111/j.1365-2249.1993.tb06498.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clerici M., Stocks N. I., Zajac R. A., Boswell R. N., Lucey D. R., Via C. S., Shearer G. M. Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging. J Clin Invest. 1989 Dec;84(6):1892–1899. doi: 10.1172/JCI114376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dalgleish A. G. The pathogenesis of AIDS: classical and alternative views. J R Coll Physicians Lond. 1992 Apr;26(2):152–158. [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Groux H., Torpier G., Monté D., Mouton Y., Capron A., Ameisen J. C. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. J Exp Med. 1992 Feb 1;175(2):331–340. doi: 10.1084/jem.175.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. doi: 10.1073/pnas.83.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Huang M. E., Ye Y. C., Chen S. R., Chai J. R., Lu J. X., Zhoa L., Gu L. J., Wang Z. Y. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567–572. [PubMed] [Google Scholar]
  12. Iwata M., Mukai M., Nakai Y., Iseki R. Retinoic acids inhibit activation-induced apoptosis in T cell hybridomas and thymocytes. J Immunol. 1992 Nov 15;149(10):3302–3308. [PubMed] [Google Scholar]
  13. Laurent-Crawford A. G., Krust B., Muller S., Rivière Y., Rey-Cuillé M. A., Béchet J. M., Montagnier L., Hovanessian A. G. The cytopathic effect of HIV is associated with apoptosis. Virology. 1991 Dec;185(2):829–839. doi: 10.1016/0042-6822(91)90554-o. [DOI] [PubMed] [Google Scholar]
  14. Meyaard L., Otto S. A., Jonker R. R., Mijnster M. J., Keet R. P., Miedema F. Programmed death of T cells in HIV-1 infection. Science. 1992 Jul 10;257(5067):217–219. doi: 10.1126/science.1352911. [DOI] [PubMed] [Google Scholar]
  15. Meyaard L., Schuitemaker H., Miedema F. T-cell dysfunction in HIV infection: anergy due to defective antigen-presenting cell function? Immunol Today. 1993 Apr;14(4):161–164. doi: 10.1016/0167-5699(93)90279-T. [DOI] [PubMed] [Google Scholar]
  16. Mosier D. E., Gulizia R. J., MacIsaac P. D., Torbett B. E., Levy J. A. Rapid loss of CD4+ T cells in human-PBL-SCID mice by noncytopathic HIV isolates. Science. 1993 Apr 30;260(5108):689–692. doi: 10.1126/science.8097595. [DOI] [PubMed] [Google Scholar]
  17. Newell M. K., Haughn L. J., Maroun C. R., Julius M. H. Death of mature T cells by separate ligation of CD4 and the T-cell receptor for antigen. Nature. 1990 Sep 20;347(6290):286–289. doi: 10.1038/347286a0. [DOI] [PubMed] [Google Scholar]
  18. Pantaleo G., Graziosi C., Demarest J. F., Butini L., Montroni M., Fox C. H., Orenstein J. M., Kotler D. P., Fauci A. S. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. doi: 10.1038/362355a0. [DOI] [PubMed] [Google Scholar]
  19. Poli G., Kinter A. L., Justement J. S., Bressler P., Kehrl J. H., Fauci A. S. Retinoic acid mimics transforming growth factor beta in the regulation of human immunodeficiency virus expression in monocytic cells. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2689–2693. doi: 10.1073/pnas.89.7.2689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Russell J. H., White C. L., Loh D. Y., Meleedy-Rey P. Receptor-stimulated death pathway is opened by antigen in mature T cells. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2151–2155. doi: 10.1073/pnas.88.6.2151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schnittman S. M., Psallidopoulos M. C., Lane H. C., Thompson L., Baseler M., Massari F., Fox C. H., Salzman N. P., Fauci A. S. The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science. 1989 Jul 21;245(4915):305–308. doi: 10.1126/science.2665081. [DOI] [PubMed] [Google Scholar]
  22. Smith M. A., Parkinson D. R., Cheson B. D., Friedman M. A. Retinoids in cancer therapy. J Clin Oncol. 1992 May;10(5):839–864. doi: 10.1200/JCO.1992.10.5.839. [DOI] [PubMed] [Google Scholar]
  23. Suda T., Takahashi T., Golstein P., Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993 Dec 17;75(6):1169–1178. doi: 10.1016/0092-8674(93)90326-l. [DOI] [PubMed] [Google Scholar]
  24. Szawlowski P. W., Hanke T., Randall R. E. Sequence homology between HIV-1 gp120 and the apoptosis mediating protein Fas. AIDS. 1993 Jul;7(7):1018–1018. doi: 10.1097/00002030-199307000-00019. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Turpin J. A., Vargo M., Meltzer M. S. Enhanced HIV-1 replication in retinoid-treated monocytes. Retinoid effects mediated through mechanisms related to cell differentiation and to a direct transcriptional action on viral gene expression. J Immunol. 1992 Apr 15;148(8):2539–2546. [PubMed] [Google Scholar]
  27. Ucker D. S., Meyers J., Obermiller P. S. Activation-driven T cell death. II. Quantitative differences alone distinguish stimuli triggering nontransformed T cell proliferation or death. J Immunol. 1992 Sep 1;149(5):1583–1592. [PubMed] [Google Scholar]
  28. Warrell R. P., Jr, de Thé H., Wang Z. Y., Degos L. Acute promyelocytic leukemia. N Engl J Med. 1993 Jul 15;329(3):177–189. doi: 10.1056/NEJM199307153290307. [DOI] [PubMed] [Google Scholar]
  29. Wesselborg S., Janssen O., Kabelitz D. Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells. J Immunol. 1993 May 15;150(10):4338–4345. [PubMed] [Google Scholar]
  30. Yang Y., Vacchio M. S., Ashwell J. D. 9-cis-retinoic acid inhibits activation-driven T-cell apoptosis: implications for retinoid X receptor involvement in thymocyte development. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6170–6174. doi: 10.1073/pnas.90.13.6170. [DOI] [PMC free article] [PubMed] [Google Scholar]

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