1887

Abstract

Interleukin-10 (IL-10), a product of T lymphocytes, B cells and macrophages, participates in Th-2 immune responses and modulates macrophage functions including possible interactions with pathogens. We have found that Chinese hamster ovary cell-derived human recombinant (hr) IL-10 inhibits human immunodeficiency virus type 1 strains Ada and Ba-L (HIV-1 and HIV-l) replication in primary tissue culture- derived macrophages in a dose-dependent manner. Inhibition by IL-10 treatment (> 5 U/ml) was effective 72 h before or 24 h after infection and cytokine activity blocked by anti-hrIL-10 antibody (19F1), or lost after heat inactivation of IL-10. Viral production was measured by determining p24 and reverse transcriptase levels while reverse transcription kinetics for the long terminal repeat (LTR) and were assessed at timed intervals after infection and quantified by P endlabelling. IL-10 inhibited early steps of infection without modulating cell surface CD4 levels. The onset of LTR reverse transcription was delayed by 4 to 8 h and the number of LTR transcripts was decreased by 77% at 24 h and by 87 % 48 h after infection. IL-10 effects were reversible; after cytokine washout, cells treated before infection showed lower levels of virus compared with those treated after infection. IL-10 biological activity was confirmed in three virus-independent assays. These results demonstrate IL-10 decreases HIV-1 reverse transcription upon macrophage infection and subsequently mediates viral latency Therefore, IL-10 may be involved in the effective control of HIV-1-infected macrophages

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1994-12-01
2024-04-26
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References

  1. Chehimi J., Starr S. E., Frank I., D’Andrea A., Ma X., Macgregor R. R., Sennelier J., Trinchieri G. 1994; Impaired Interleukin 12 production in human immunodeficiency virus-infected patients. Journal of Experimental Medicine 179:1361–1366
    [Google Scholar]
  2. Clerici M., Shearer G. M. 1993; A Th1 to Th2 switch is a critical step in the etiology of HIV infection. Immunology Today 14:107–111
    [Google Scholar]
  3. Clerici M., Wynn T. A., Berzofsky J. A., Blatt S. P., Hendrix C. W., Sher A., Coffman R. L., Shearer G. M. 1994; Role of interleukin 10 (IL-10) in T helper cell dysfunction in asymptomatic individuals infected with the human immunodeficiency virus (HIV- 1). Journal of Clinical Investigation 93:768–775
    [Google Scholar]
  4. Clouse K. A., Powel D., Washington I., Poli G., Strebel K., Farrar W., Barstad P., Kovacs J., Fauci A. S., Folk T. M. 1989; Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. Journal of Immunology 142:431–438
    [Google Scholar]
  5. Collin M., Gordon S. 1994; The kinetics of human immunodeficiency virus reverse transcription are slower in primary human macrophages than in lymphoid cells. Virology 200:114–120
    [Google Scholar]
  6. Collin M., Herbein G., Montaner L. J., Gordon S. 1993; PCR analysis of HIV-1 infection of macrophages: virus entry is CD4- dependent. Journal of Research in Virology 144:13–19
    [Google Scholar]
  7. D’Andrea A., Aste-Amezaga M., Valiente N. M., Ma X., Kubin M., Trinchieri G. 1993; Interleukin 10 (IL-10) inhibits human lymphocyte interferon-γ production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. Journal of Experimental Medicine 178:1041–1048
    [Google Scholar]
  8. De Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., De Vries J. E. 1991; Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. Journal of Experimental Medicine 174:1209–1220
    [Google Scholar]
  9. De Waal Malefyt R., Yssel H., Roncarolo M. -G., Spits H., De Vries J. E. 1992; Interleukin-10. Current Opinion in Immunology 4:314–320
    [Google Scholar]
  10. Embretson J., Zupancic M., Ribas J. L., Burke A., Racs P., Tenner-Racs K., Haase A. 1993; Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature; London: 362359–362
    [Google Scholar]
  11. Fan J., Bass H. Z., Fahey J. L. 1993; Elevated IFN-γ and decreased IL-2 gene expression are associated with HIV infection. Journal of Immunology 151:5031–5040
    [Google Scholar]
  12. Fauci A. S. 1993; Multifactional nature of human immunodeficiency virus disease: implications for therapy. Science 262:1011–1018
    [Google Scholar]
  13. Gartner S., Markovits P., Markovits D. M., Kaplan M. H., Gallo R. C., Popovic M. 1986; The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215–219
    [Google Scholar]
  14. Gazzinelli R. T., Oswald I. P., James S. L., Sher A. 1992; IL- 10 inhibits parasite killing and nitrogen oxide production by IFN-γ-activated macrophages. Journal of Immunology 148:1792–1797
    [Google Scholar]
  15. Graziosi C., Pantaleo G., Gantt K. R., Demarest J. F., Cohen O. J., Vaccarezza M., Fauci A. S. 1994; Comparative analysis of cytokine expression in peripheral blood and lymph nodes of patients with F1IV infection: lack of evidence for Th-1 versus Th-2 imbalance. Journal of Cellular Biochemistry Abstract supplement 18B 149:
    [Google Scholar]
  16. Gendelman H. E., Orenstein J. M., Martin M. A., Ferrua C., Mitra R., Phipps T., Wahl L. A., Lane H. C., Fauci A. S., Burke D. S. 1988; Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. Journal of Experimental Medicine 167:1428–1441
    [Google Scholar]
  17. Gendelman H. E., Orenstein J. M., Baca L. M., Weiser B., Burgers FI., Kalter D. C., Meltzer M. S. 1989; The macrophage in the persistence and pathogenesis of HIV infection. AIDS 3:475–495
    [Google Scholar]
  18. Herbein G., Keshav S., Collin M., Montaner L. J., Gordon S. 1994; HIV-1 induces tumor necrosis factor and IL-1 gene expression in primary human macrophages independent of productive infection. Clinical Experimental Immunology 95:442–449
    [Google Scholar]
  19. Kazazi F., Mathijs J. M., Chang J., Malafiej P., Lopez A., Dowton D., Sorrell T. C., Vadas M. A., Cunningham A. L. 1992; Recombinant interleukin 4 stimulates human immunodeficiency virus production by infected monocytes and macrophages. Journal of General Virology 73:941–949
    [Google Scholar]
  20. Kinter A. L., Poli G., Fox L., Goletti D., Fauci A. S. 1994; Endogenous cytokines drive HIV-1 replication in primary human peripheral blood mononuclear cells stimulated with interleukin-2 in absence of mitogens. Journal of Cellular Biochemistry Abstract supplement 18B 134:
    [Google Scholar]
  21. Mikovits J. A., Lohrey N. C., Schulof R., Courtless J., Ruscetti F. W. 1992; Activation of infectious virus from latent human immunodeficiency virus infection of monocytes in vivo. Journal of Clinical Investigation 90:1486–1491
    [Google Scholar]
  22. Montaner L. J., Doyle A. G., Collin M., Herbein G., Illei P., James W., Minty A., Caput D., Ferrara P., Gordon S. 1993; Interleukin 13 inhibits human immunodeficiency virus type 1 production in primary blood-derived human macrophages in vitro. Journal of Experimental Medicine 178:743–747
    [Google Scholar]
  23. Oswald I. P., Gazzinelli R. T., Sher A., James S. L. 1992; IL- 10 synergizes with IL-4 and transforming growth factor-β to inhibit macrophage cytotoxic activity. Journal of Immunology 148:3578–3582
    [Google Scholar]
  24. Pantaleo G., Graziosi C., Demarest J. F., Butini L., Montroni M., Fox C. H., Orenstein J. M., Kotler D. P., Fauci A. S. 1993; HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature; London: 362355–358
    [Google Scholar]
  25. Poli G., Fauci A. S. 1992; The role of monocyte/macrophages and cytokines in the pathogenesis of HIV infection. Pathobiology 60:246–252
    [Google Scholar]
  26. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. 1984; Detection, isolation and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497–500
    [Google Scholar]
  27. Popovic M., Gartner S. 1987; Isolation of HIV-1 from monocytes but not T lymphocytes. Lancet ii:916
    [Google Scholar]
  28. Prete G. D., Carli M. D., Almerigogna F., Guidizi M. G., Biagiotti R., Romagnani S. 1993; Human IL-10 produced by both type 1 helper (Thl) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. Journal of Immunology 150:353–360
    [Google Scholar]
  29. Ralph P., Nakoinz I., Sampson Johannes A., Fong S., Lowe D., Min H. Y., Lin L. 1992; IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. Journal of Immunology 148:808–814
    [Google Scholar]
  30. Saville M. W., Taga K., Foli A., Broder S., Tosato G., Yarchoan R. 1994; Interleukin-10 suppresses human immunodeficiency virus-1 replication in vitro in cells of the monocyte/ macrophage lineage. Blood 83:3591–3599
    [Google Scholar]
  31. Schuitemaker H., Kootstra N. A., De Goede R. E. Y., De Wolf F., Miedema F., Tersmette M. 1991; Monocytotropic human immunodeficiency virus type 1 (HIV-1) variants detectable at all stages of HIV-1 infection lack T-cell line tropism and syncytium- inducing ability in primary T-cell culture. Journal of Virology 65:356–363
    [Google Scholar]
  32. Schuitemaker H., Koot M., Kootstra N. A., Dercksen M. W., Degoede R. E. Y., Van Steenwijk R. P., Lange J. M. A., Schattenkerk J. K. M. E., Miedema F., Tersmette M. 1992a; Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-tropic virus population. Journal of Virology 66:1354–1360
    [Google Scholar]
  33. Schuitemaker H., Kootstra N. A., Koppelman M. H. G. M., Bruisten S. M., Huisman H. G., Tersmette M., Miedema F. 1992b; Proliferation-dependent HIV-1 infection of monocytes occurs during differentiation into macrophages. Journal of Clinical Investigation 89:1154–1160
    [Google Scholar]
  34. Te Velde A. A., De Waal Malefyt R., Huijbens R. J. F., Devries J. E., Figdor C. G. 1992; IL-10 stimulates monocyte FcγR surface expression and cytotoxic activity. Journal of Immunology 149:4048–4052
    [Google Scholar]
  35. Trauger R. J., Giermakowska W. K., Ferre F., Duffy P. C., Wallance M. R., Lewis D. E., Beecham H. J., Burnett K. G., Jensen F. C., Carlo D. J. 1993; Cell-mediated immunity to HIV-1 in Walter Reed stages 1–6 individuals: correlation with viral burden. Immunology 78:611–615
    [Google Scholar]
  36. Weissman D., Poli G., Fauci A. S. 1994; Interleukin 10 blocks HIV replication in macrophages by inhibiting the autocrine loop of TNF-a and IL-6 induction of virus. AIDS Research and Human Retroviruses (in press)
    [Google Scholar]
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