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. 1996 Apr;87(4):528–534. doi: 10.1046/j.1365-2567.1996.514588.x

Chimpanzee dendritic cells with potent immunostimulatory function can be propagated from peripheral blood.

S M Barratt-Boyes 1, R A Henderson 1, O J Finn 1
PMCID: PMC1384129  PMID: 8675205

Abstract

We have established dendritic cell (DC) cultures from chimpanzee peripheral blood mononuclear cells (PBMC) by using recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and rh interleukin-4 (IL-4) and demonstrate that these cells have all the characteristics of DC as described for other species. We consistently can obtain 1 x 10(7) DC per 100 ml of blood, a yield of 5% DC as compared to 0.1 to 0.5% DC reported in fresh human PBMC. The cultured DC have a varied morphology with typical cytoplasmic extensions. Phenotypically, the blood-derived DC lack expression of most lineage antigens, but express CD83, an antigen specifically expressed on human blood DC. Chimpanzee DC express very high levels of major histocompatability complex class II antigens, adhesion and costimulatory molecules. Consistent with this phenotype of a powerful antigen-presenting cell, chimpanzee DC generate allogeneic mixed leukocyte responses 15 to 20 times more potent than that elicited by macrophages, Epstein-Barr virus-transformed lymphoblasts and fresh PBMC. In addition, chimpanzee DC very efficiently present tetanus toxoid to PBMC-derived CD4+ T cells as compared to macrophages and PBMC. The DC generated by culturing chimpanzee PBMC with rhGM-CSF and rhIL-4 thus closely resemble human blood-derived DC propagated in the same manner. This technology provides a powerful animal model with which to apply DC to clinical studies with relevance to human disease. In particular, chimpanzee DC can be tested as immunotherapeutic agents for cancer, and be studied in relation to the pathogenesis of human immunodeficiency virus (HIV) infection.

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Selected References

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  1. Austyn J. M., Larsen C. P. Migration patterns of dendritic leukocytes. Implications for transplantation. Transplantation. 1990 Jan;49(1):1–7. doi: 10.1097/00007890-199001000-00001. [DOI] [PubMed] [Google Scholar]
  2. Bhargava A. K., Woitach J. T., Davidson E. A., Bhavanandan V. P. Cloning and cDNA sequence of a bovine submaxillary gland mucin-like protein containing two distinct domains. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6798–6802. doi: 10.1073/pnas.87.17.6798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cameron P. U., Freudenthal P. S., Barker J. M., Gezelter S., Inaba K., Steinman R. M. Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. Science. 1992 Jul 17;257(5068):383–387. doi: 10.1126/science.1352913. [DOI] [PubMed] [Google Scholar]
  4. Caux C., Dezutter-Dambuyant C., Schmitt D., Banchereau J. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature. 1992 Nov 19;360(6401):258–261. doi: 10.1038/360258a0. [DOI] [PubMed] [Google Scholar]
  5. Caux C., Vanbervliet B., Massacrier C., Azuma M., Okumura K., Lanier L. L., Banchereau J. B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med. 1994 Nov 1;180(5):1841–1847. doi: 10.1084/jem.180.5.1841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen L., Ashe S., Brady W. A., Hellström I., Hellström K. E., Ledbetter J. A., McGowan P., Linsley P. S. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell. 1992 Dec 24;71(7):1093–1102. doi: 10.1016/s0092-8674(05)80059-5. [DOI] [PubMed] [Google Scholar]
  7. Egner W., McKenzie J. L., Smith S. M., Beard M. E., Hart D. N. Identification of potent mixed leukocyte reaction-stimulatory cells in human bone marrow. Putative differentiation stage of human blood dendritic cells. J Immunol. 1993 Apr 1;150(7):3043–3053. [PubMed] [Google Scholar]
  8. Flamand V., Sornasse T., Thielemans K., Demanet C., Bakkus M., Bazin H., Tielemans F., Leo O., Urbain J., Moser M. Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo. Eur J Immunol. 1994 Mar;24(3):605–610. doi: 10.1002/eji.1830240317. [DOI] [PubMed] [Google Scholar]
  9. Hart D. N., Starling G. C., Calder V. L., Fernando N. S. B7/BB-1 is a leucocyte differentiation antigen on human dendritic cells induced by activation. Immunology. 1993 Aug;79(4):616–620. [PMC free article] [PubMed] [Google Scholar]
  10. Inaba K., Inaba M., Romani N., Aya H., Deguchi M., Ikehara S., Muramatsu S., Steinman R. M. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992 Dec 1;176(6):1693–1702. doi: 10.1084/jem.176.6.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Inaba K., Steinman R. M., Pack M. W., Aya H., Inaba M., Sudo T., Wolpe S., Schuler G. Identification of proliferating dendritic cell precursors in mouse blood. J Exp Med. 1992 May 1;175(5):1157–1167. doi: 10.1084/jem.175.5.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Knight S. C., Hunt R., Dore C., Medawar P. B. Influence of dendritic cells on tumor growth. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4495–4497. doi: 10.1073/pnas.82.13.4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Langhoff E., Terwilliger E. F., Bos H. J., Kalland K. H., Poznansky M. C., Bacon O. M., Haseltine W. A. Replication of human immunodeficiency virus type 1 in primary dendritic cell cultures. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7998–8002. doi: 10.1073/pnas.88.18.7998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Larsen C. P., Ritchie S. C., Pearson T. C., Linsley P. S., Lowry R. P. Functional expression of the costimulatory molecule, B7/BB1, on murine dendritic cell populations. J Exp Med. 1992 Oct 1;176(4):1215–1220. doi: 10.1084/jem.176.4.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Liu Y., Linsley P. S. Costimulation of T-cell growth. Curr Opin Immunol. 1992 Jun;4(3):265–270. doi: 10.1016/0952-7915(92)90075-p. [DOI] [PubMed] [Google Scholar]
  16. Lu L., Hsieh M., Oriss T. B., Morel P. A., Starzl T. E., Rao A. S., Thomson A. W. Generation of DC from mouse spleen cell cultures in response to GM-CSF: immunophenotypic and functional analyses. Immunology. 1995 Jan;84(1):127–134. [PMC free article] [PubMed] [Google Scholar]
  17. Macatonia S. E., Lau R., Patterson S., Pinching A. J., Knight S. C. Dendritic cell infection, depletion and dysfunction in HIV-infected individuals. Immunology. 1990 Sep;71(1):38–45. [PMC free article] [PubMed] [Google Scholar]
  18. Pope M., Betjes M. G., Romani N., Hirmand H., Cameron P. U., Hoffman L., Gezelter S., Schuler G., Steinman R. M. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell. 1994 Aug 12;78(3):389–398. doi: 10.1016/0092-8674(94)90418-9. [DOI] [PubMed] [Google Scholar]
  19. Reid C. D., Stackpoole A., Meager A., Tikerpae J. Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow. J Immunol. 1992 Oct 15;149(8):2681–2688. [PubMed] [Google Scholar]
  20. Ringler D. J., Hancock W. W., King N. W., Murphy G. F. Characterization of nonhuman primate epidermal and dermal dendritic cells with monoclonal antibodies. A study of Langerhans cells and indeterminate cells in the rhesus monkey. Lab Invest. 1987 Mar;56(3):313–320. [PubMed] [Google Scholar]
  21. Romani N., Gruner S., Brang D., Kämpgen E., Lenz A., Trockenbacher B., Konwalinka G., Fritsch P. O., Steinman R. M., Schuler G. Proliferating dendritic cell progenitors in human blood. J Exp Med. 1994 Jul 1;180(1):83–93. doi: 10.1084/jem.180.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Romani N., Koide S., Crowley M., Witmer-Pack M., Livingstone A. M., Fathman C. G., Inaba K., Steinman R. M. Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. J Exp Med. 1989 Mar 1;169(3):1169–1178. doi: 10.1084/jem.169.3.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sallusto F., Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994 Apr 1;179(4):1109–1118. doi: 10.1084/jem.179.4.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Santiago-Schwarz F., Belilos E., Diamond B., Carsons S. E. TNF in combination with GM-CSF enhances the differentiation of neonatal cord blood stem cells into dendritic cells and macrophages. J Leukoc Biol. 1992 Sep;52(3):274–281. [PubMed] [Google Scholar]
  25. Schwartz R. H. A cell culture model for T lymphocyte clonal anergy. Science. 1990 Jun 15;248(4961):1349–1356. doi: 10.1126/science.2113314. [DOI] [PubMed] [Google Scholar]
  26. Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
  27. Symington F. W., Brady W., Linsley P. S. Expression and function of B7 on human epidermal Langerhans cells. J Immunol. 1993 Feb 15;150(4):1286–1295. [PubMed] [Google Scholar]
  28. Szabolcs P., Moore M. A., Young J. W. Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34+ bone marrow precursors cultured with c-kit ligand, granulocyte-macrophage colony-stimulating factor, and TNF-alpha. J Immunol. 1995 Jun 1;154(11):5851–5861. [PubMed] [Google Scholar]
  29. 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]
  30. Zhou L. J., Tedder T. F. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J Immunol. 1995 Apr 15;154(8):3821–3835. [PubMed] [Google Scholar]

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