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. 1990 Mar;85(3):955–961. doi: 10.1172/JCI114525

Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peripheral blood dendritic cells in vitro.

S Markowicz 1, E G Engleman 1
PMCID: PMC296516  PMID: 2179270

Abstract

Interest in human dendritic cells (DC) has been heightened recently by the discovery that this cell type is a primary target of the human immunodeficiency virus, the causative agent of AIDS. DC are bone marrow-derived cells with an extraordinarily potent ability to promote the immunological activity of T lymphocytes. Unfortunately, since DC constitute less than 0.5% of peripheral blood mononuclear cells and die within a few days of their isolation, they are not readily accessible to study. We report here that granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine with well-recognized effects on granulocyte and macrophage maturation, profoundly affects the morphology and viability of DC isolated from peripheral blood. GM-CSF not only promotes DC survival but also induces DC differentiation to mobile, reversibly adherent cells with long-branched projections. DC cultured in GM-CSF survive for up to 6 wk and retain their ability to stimulate the proliferation of T cells in allogeneic and autologous mixed leukocyte reactions.

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Selected References

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

  1. Brandt S. J., Peters W. P., Atwater S. K., Kurtzberg J., Borowitz M. J., Jones R. B., Shpall E. J., Bast R. C., Jr, Gilbert C. J., Oette D. H. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation. N Engl J Med. 1988 Apr 7;318(14):869–876. doi: 10.1056/NEJM198804073181401. [DOI] [PubMed] [Google Scholar]
  2. Clark S. C., Kamen R. The human hematopoietic colony-stimulating factors. Science. 1987 Jun 5;236(4806):1229–1237. doi: 10.1126/science.3296190. [DOI] [PubMed] [Google Scholar]
  3. Engleman E. G., Benike C. J., Grumet F. C., Evans R. L. Activation of human T lymphocyte subsets: helper and suppressor/cytotoxic T cells recognize and respond to distinct histocompatibility antigens. J Immunol. 1981 Nov;127(5):2124–2129. [PubMed] [Google Scholar]
  4. Groopman J. E., Mitsuyasu R. T., DeLeo M. J., Oette D. H., Golde D. W. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med. 1987 Sep 3;317(10):593–598. doi: 10.1056/NEJM198709033171003. [DOI] [PubMed] [Google Scholar]
  5. Hauser C., Katz S. I. Activation and expansion of hapten- and protein-specific T helper cells from nonsensitized mice. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5625–5628. doi: 10.1073/pnas.85.15.5625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Heufler C., Koch F., Schuler G. Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med. 1988 Feb 1;167(2):700–705. doi: 10.1084/jem.167.2.700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Inaba K., Steinman R. M. Protein-specific helper T-lymphocyte formation initiated by dendritic cells. Science. 1985 Aug 2;229(4712):475–479. doi: 10.1126/science.3160115. [DOI] [PubMed] [Google Scholar]
  8. Macatonia S. E., Taylor P. M., Knight S. C., Askonas B. A. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro. J Exp Med. 1989 Apr 1;169(4):1255–1264. doi: 10.1084/jem.169.4.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Patterson S., Knight S. C. Susceptibility of human peripheral blood dendritic cells to infection by human immunodeficiency virus. J Gen Virol. 1987 Apr;68(Pt 4):1177–1181. doi: 10.1099/0022-1317-68-4-1177. [DOI] [PubMed] [Google Scholar]
  10. Sieff C. A. Hematopoietic growth factors. J Clin Invest. 1987 Jun;79(6):1549–1557. doi: 10.1172/JCI112988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sieff C. A., Tsai S., Faller D. V. Interleukin 1 induces cultured human endothelial cell production of granulocyte-macrophage colony-stimulating factor. J Clin Invest. 1987 Jan;79(1):48–51. doi: 10.1172/JCI112806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Steinman R. M. Cytokines amplify the function of accessory cells. Immunol Lett. 1988 Mar;17(3):197–202. doi: 10.1016/0165-2478(88)90028-4. [DOI] [PubMed] [Google Scholar]
  13. Steinman R. M., Nussenzweig M. C. Dendritic cells: features and functions. Immunol Rev. 1980;53:127–147. doi: 10.1111/j.1600-065x.1980.tb01042.x. [DOI] [PubMed] [Google Scholar]
  14. Tschachler E., Groh V., Popovic M., Mann D. L., Konrad K., Safai B., Eron L., diMarzo Veronese F., Wolff K., Stingl G. Epidermal Langerhans cells--a target for HTLV-III/LAV infection. J Invest Dermatol. 1987 Feb;88(2):233–237. doi: 10.1111/1523-1747.ep12525402. [DOI] [PubMed] [Google Scholar]
  15. Van Voorhis W. C., Hair L. S., Steinman R. M., Kaplan G. Human dendritic cells. Enrichment and characterization from peripheral blood. J Exp Med. 1982 Apr 1;155(4):1172–1187. doi: 10.1084/jem.155.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Witmer-Pack M. D., Olivier W., Valinsky J., Schuler G., Steinman R. M. Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells. J Exp Med. 1987 Nov 1;166(5):1484–1498. doi: 10.1084/jem.166.5.1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wybran J., Chantler S., Fudenberg H. H. Isolation of normal T cells in chronic lymphatic leukaemia. Lancet. 1973 Jan 20;1(7795):126–129. doi: 10.1016/s0140-6736(73)90196-7. [DOI] [PubMed] [Google Scholar]
  18. Young J. W., Steinman R. M. Accessory cell requirements for the mixed-leukocyte reaction and polyclonal mitogens, as studied with a new technique for enriching blood dendritic cells. Cell Immunol. 1988 Jan;111(1):167–182. doi: 10.1016/0008-8749(88)90061-5. [DOI] [PubMed] [Google Scholar]
  19. Zvaifler N. J., Steinman R. M., Kaplan G., Lau L. L., Rivelis M. Identification of immunostimulatory dendritic cells in the synovial effusions of patients with rheumatoid arthritis. J Clin Invest. 1985 Aug;76(2):789–800. doi: 10.1172/JCI112036. [DOI] [PMC free article] [PubMed] [Google Scholar]

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