1887

Abstract

The mechanism for the gradual loss of CD4 T lymphocytes and the development of the slowly progressive inflammatory/degenerative lesions that accompany human immunodeficiency virus infection are poorly understood. Using the Simian immunodeficiency virus (SIV) macaque model of AIDS, we found that persistently infected primary macrophages fuse with primary activated CD4 lymphocytes and that this interaction results in production of tumour necrosis factor-α (TNFα) and interleukin 6 (IL-6). An earlier report had shown that SIV-infected macaque macrophages fuse with CEM174 cells (a human CD4 cell line) and cause their lysis. In the present report, we have shown that TNF-α and IL-6 are also produced during the early stages of this interaction. Data from cocultivation of infected macrophages with several CD4 T cell lines, including CEM174, suggested that the cytokines are produced by the T cells, and that cytokine production is restricted to those cells which not only express CD4, but are also capable of fusing with the infected macrophages. These data suggest that infected macrophages could fuse with and eliminate activated CD4 lymphocytes and, during this interaction, release cytokines, which would contribute to the degenerative and inflammatory lesions characteristic of this disease.

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1992-05-01
2021-10-20
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References

  1. Aarden L. A., De Groot E. R., Schaaf O. L., Lansdorp P. M. 1987; Production of hybridoma growth factor by human monocytes. European Journal of Immunology 17:1411–1416
    [Google Scholar]
  2. Cheung S. C., Chattopadhyay S. K., Hartley J. W., Morse H. C., Pitha P. M. 1991; Aberrant expression of cytokine genes in peritoneal macrophages from mice infected with LP-BM5 MuLV, a murine model of AIDS. Journal of Immunology 746121–127
    [Google Scholar]
  3. Desrosiers R. C. 1988; Simian immunodeficiency viruses. Annual Review of Microbiology 42:607–625
    [Google Scholar]
  4. Desrosiers R. C. 1990; Simian immunodeficiency viruses. Annual Review of Immunology 8:557–578
    [Google Scholar]
  5. Eilbott D. J., Peress N., Burger H., LaNeve D., Orenstein J., Gendelman H. E., Seidman R., Weiser B. 1989; Human immunodeficiency virus type 1 in spinal cords of acquired immunodeficiency syndrome patients with myelopathy: expression and replication in macrophages. Proceedings of the National Academy of Sciences, U.S.A. 86:3337–3341
    [Google Scholar]
  6. Fauci A. S. 1988; The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 239:617–622
    [Google Scholar]
  7. Fox C. H., Kotler D., Tierney A., Wilson C. S., Fauci A. S. 1989; Detection of HIV-1 RNA in the lamina propria of patients with AIDS and gastrointestinal disease. Journal of Infectious Diseases 159:467–471
    [Google Scholar]
  8. Gorrell M. D., Miller H. R. P., Brandon M. R. 1988; Lymphocyte phenotypes in the abomasal mucosa of sheep infected with Haemonchus contortus. Parasite Immunology 10:661–674
    [Google Scholar]
  9. Hansen M. B., Nielsen S. E., Berg K. 1989; Reexamination and further development of a precise and rapid dye method for measuring cell growth/cell killing. Journal of Immunological Methods 119:203–210
    [Google Scholar]
  10. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. 1986; Detection of lymphocytes expressing human T-lymphotrophic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proceedings of the National Academy of Sciences, U.S.A. 83:772–776
    [Google Scholar]
  11. Ho D. D., Pomerantz R. J., Kaplan J. C. 1987; Pathogenesis of infection with human immunodeficiency virus. New England Journal of Medicine 317:278–286
    [Google Scholar]
  12. Johnson R. T., McArthur J. C., Narayan O. 1988; The neurobiology of human immunodeficiency virus infections. FASEB Journal 2:2970–2981
    [Google Scholar]
  13. Julius M. H., Simpson E., Herzenberg L. A. 1973; A rapid method for the isolation of functional thymus-derived murine lymphocytes. European Journal of Immunology 3:645–649
    [Google Scholar]
  14. Lieberman A. P., Pitha P. M., Shin H. S., Shin M. L. 1989; Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus. Proceedings of the National Academy of Sciences, U.S.A. 86:6348–6352
    [Google Scholar]
  15. McEntee M. F., Sharma D. P., Zink M. C., Adams R. J., Flexner C., Clements J. E., Narayan O. 1991; Rhesus monkey macrophages infected with simian immunodeficiency virus cause rapid lysis of CD4-bearing lymphocytes. Journal of General Virology 72:317–324
    [Google Scholar]
  16. Mage M. G. 1984; Separation of lymphocytes on antibody-coated plates. Methods in Enzymology 108:168–174
    [Google Scholar]
  17. Narayan O., Kennedy-Stoskopf S., Sheffer D., Griffin D. E., Clements J. E. 1983; Activation of caprine arthritis-encephalitis virus expression during maturation of monocytes to macrophages. Infection and Immunity 41:67–73
    [Google Scholar]
  18. Narayan O., Sheffer D., Clements J. E., Tennekoon G. 1985; Restricted replication of lentiviruses: visna viruses induce a unique interferon during interaction between lymphocytes and infected macrophages. Journal of Experimental Medicine 162:1954–1969
    [Google Scholar]
  19. Pitha P. M., Harper H. D., Pitha J. 1974; Dependence of interferon induction on cell membrane integrity. Virology 59:40–50
    [Google Scholar]
  20. Psallidopoulos M. C., Schnittman S. M., Thompson L. M., Baseler M., Fauci A. S., Lane H. C., Salzman N. P. 1989; Integrated proviral human immunodeficiency virus type 1 is present in CD4+ peripheral blood lymphocytes in healthy seropositive individuals. Journal of Virology 63:4626–4631
    [Google Scholar]
  21. Rokos K., Pauli G. 1991; Interferon induction by cell-cell interaction of HIV-infected monocytes/macrophages with lymphocytes. Research in Virology 142:221–225
    [Google Scholar]
  22. Selmaj K. W., Raine C. S. 1988; Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Annals of Neurology 23:339–346
    [Google Scholar]
  23. Selmaj K. W., Farooq M., Norton W. T., Raine C. S., Brosnan C. F. 1990; Proliferation of astrocytes in vitro in response to cytokines: a primary role for tumor necrosis factor. Journal of Immunology 144:129–135
    [Google Scholar]
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