1887

Abstract

Recent evidence suggests that T cell apoptosis could be involved in the pathogenesis of HIV infection. In addition, lymphocyte apoptosis has been described in SIV-infected macaques that developed simian AIDS. To investigate further the role of apoptosis in AIDS pathogenesis, we studied lymphocytes of HIV-2-infected cynomolgus macaques that did not develop simian AIDS. We compared apoptosis of lymphocytes from animals infected with non-pathogenic HIV-2 to that in macaques infected with pathogenic SIV. Unfractionated peripheral blood mononuclear cells of SIV- and HIV-2-infected macaques showed evidence of apoptosis by electron microscopy, flow cytometry (terminal dUTP nick end labelling) and visualization of DNA fragmentation. Between 30–50% apoptotic cells could be detected in SIV-infected animals, compared to approximately 30% in HIV-2-infected and 5–12% in uninfected monkeys. However, separation of PBMC into T cell subpopulations revealed striking differences in apoptosis between SIV- and HIV-2-infected macaques. In SIV-infected monkeys both CD4 and CD8 cells underwent apoptosis to a large extent. In contrast, in the HIV-2-infected macaques apoptosis was restricted to the CD8 cell compartment. The lack of apoptosis in CD4 cells of healthy HIV-2-infected macaques implies an important role for CD4 cell apoptosis in AIDS pathogenesis.

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1996-10-01
2024-04-27
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References

  1. Ameisen J. C. 1992; Programmed cell death and AIDS: from hypothesis to experiment. Immunology Today 13:388–391
    [Google Scholar]
  2. Ameisen J. C. 1994; Programmed cell death (apoptosis) and cell survival regulation: relevance to AIDS and cancer. AIDS 8:1197–1213
    [Google Scholar]
  3. Carbonari M., Cibati M., Pesce A. M., Sbarigia D., Grossi P., D’Offizi G., Luzi G., Fiorilli M. 1995; Frequency of provirus-bearing CD4 + cells in HIV type 1 infection correlates with extent of in vitro apoptosis of CD8 + but not of CD4 + cells. AIDS Research and Human Retroviruses 11:789–794
    [Google Scholar]
  4. Cohen J. J. 1993; Apoptosis. Immunology Today 14:126–130
    [Google Scholar]
  5. Cranage M. P., Cook N., Johnstone P., Greenaway P., Kitchin P. A., Stott E. J., Almond N., Baskerville A. 1990; SIV infection of rhesus macaques: in vitro titration of infectivity and development of an experimental vaccine. In Animal Models in AIDS pp 103–114 Edited by Schnellkens H. Amsterdam: Elsevier;
    [Google Scholar]
  6. Dittmer U., Luke W., Stahl-Hennig C., Coulibaly C., Petry H., Bodemer W., Hunsmann G., Voss G. 1994; Early helper T-cell dysfunction in SIV-but not HlV-2-infected macaques. ]oumal of Medical Primatology 23:298–303
    [Google Scholar]
  7. Estaquier J., Idziorek T., De Bels F., Barre-Sinoussi F., Hurtrel B., Aubertin A. M., Venet A., Mehtali M., Muchmore E., Michel P., Mouton Y., Girard M., Ameisen J. C. 1994; Programmed cell death and AIDS: significance of T-cell apoptosis in pathogenic and nonpathogenic primate lentiviral infections. Proceedings of the National Academy of Sciences, USA 91:9431–9435
    [Google Scholar]
  8. Gougeon M.-L., Montagnier L. 1993; Apoptosis in Aids. Science 260:1269–1270
    [Google Scholar]
  9. Gougeon M.-L., Colizzi V., Dalgleish A., Montagnier L. 1993a; New concepts in AIDS pathogenesis. AIDS Research and Human Retroviruses 9:287–289
    [Google Scholar]
  10. Gougeon M. L., Garcia S., Heeney J., Tschopp R., Lecoeur H., Guetard D., Rame V., Dauguet C., Montagnier L. 1993b; Programmed cell death in AIDS-related HIV and SIV infections. AIDS Research and Human Retroviruses 9:553–563
    [Google Scholar]
  11. Heeney J. L. 1995; AIDS: a disease of impaired Th-cell renewal?. Immunology Today 16:515–520
    [Google Scholar]
  12. Lüke W., Coulibaly C., Dittmer U., Voss G., Oesterle R., Makoschey B., Sauermann S., Jurkiewicz E., Stahl-Hennig C., Petry H., Hunsmann G. 1996; Simian immunodeficiency virus (SIV) gp130-oligomers protect rhesus macaques (Macaca mulatto) against the infection with SIVmac32H grown on T-cells or derived ex vivo . Virology 216:444–450
    [Google Scholar]
  13. Petry H., Dittmer U., Stahl-Hennig C., Coulibaly C., Makoschey B., Fuchs D., Wachter H., Tolle T., Morys-Wortmann G., Kaup F.-J., Jurkiewicz E., Luke W., Hunsmann G. 1995; Reactivation of HIV-2 in macaques after SIVmac superinfection. Journal of Virology 69:1564–1574
    [Google Scholar]
  14. Putkonen P., Bottiger B., Warstedt K., Thorstensson R., Albert J., Biberfeld G. 1989; Experimental infection of cynomolgus monkeys (Macaca fascicularis) with HIV-2. Journal of AIDS 2:366–373
    [Google Scholar]
  15. Schäffner J.-W., Dittmer U., Otteken A., Coulibaly C., Bodemer W., Voss G., Hunsmann G. 1994; Comparison of humoral immunity and induction of proliferating T lymphocytes in vaccinia virus-infected rabbits and rhesus macaques. American Journal of Veterinary Research 55:1250–1255
    [Google Scholar]
  16. Schuitemaker H., Meyaard L., Kootstra N. A., Dubbes R., Otto S. A., Tersmette M., Heeney J. L., Miedema F. 1993; Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants. Journal of Infectious Diseases 168:1140–1147
    [Google Scholar]
  17. Stahl-Hennig C., Voss G., Dittmer U., Coulibaly C., Petry H., Makoschey B., Cranage M. P., Aubertin A. M., Luke W., Hunsmann G. 1993; Protection of monkeys by a split vaccine against SIVmac depends upon biological properties of the challenge virus. AIDS 7:787–795
    [Google Scholar]
  18. Voss G., Hunsmann G. 1993; Cellular immune response to SIVmac and HIV-2 in macaques: model for the human HIV-1 infection. Journal of Acquired Immunodeficiency Syndromes 6:969–976
    [Google Scholar]
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