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. 1994 Jul;82(3):487–493.

Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature.

U O'Doherty 1, M Peng 1, S Gezelter 1, W J Swiggard 1, M Betjes 1, N Bhardwaj 1, R M Steinman 1
PMCID: PMC1414873  PMID: 7525461

Abstract

Two subsets of dendritic cells, differing in T-cell stimulatory function, have been purified directly from human blood. Both subsets are positive for major histocompatibility complex (MHC) class II expression and negative for lineage-specific antigens (e.g. CD3, CD14, CD16, CD19 negative), but are separated by exploiting differences in expression of the beta 2-integrin, CD11c. The CD11c-negative subset is functionally immature, requiring monocyte-derived cytokines to develop into typical dendritic cells. The CD11c-positive subset has potent T-cell stimulating activity and expresses the activation antigen CD45RO, unlike its immature counterpart. However, these mature cells only develop typical dendritic morphology and high levels of MHC proteins and adhesins after a period of culture independent of exogenous cytokines. Although the freshly isolated mature dendritic cells resemble monocytes in cytospin preparations, the former lack CD14 and have a much stronger primary T-cell stimulatory capacity. We hypothesize that the CD11c-negative immature cells are marrow-derived precursors to tissue dendritic cells, such as epidermal Langerhans' cells, while the CD11c-positive cells are derived from tissues where they have been activated by antigen, and are en route to the spleen or lymph nodes to stimulate T-cell responses there.

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Selected References

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  1. Bilyk N., Holt P. G. Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor. J Exp Med. 1993 Jun 1;177(6):1773–1777. doi: 10.1084/jem.177.6.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Crowley M. T., Inaba K., Witmer-Pack M. D., Gezelter S., Steinman R. M. Use of the fluorescence activated cell sorter to enrich dendritic cells from mouse spleen. J Immunol Methods. 1990 Oct 4;133(1):55–66. doi: 10.1016/0022-1759(90)90318-p. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Faustman D. L., Steinman R. M., Gebel H. M., Hauptfeld V., Davie J. M., Lacy P. E. Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3864–3868. doi: 10.1073/pnas.81.12.3864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fleit H. B., Wright S. D., Unkeless J. C. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. doi: 10.1073/pnas.79.10.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Frelinger J. G., Hood L., Hill S., Frelinger J. A. Mouse epidermal Ia molecules have a bone marrow origin. Nature. 1979 Nov 15;282(5736):321–323. doi: 10.1038/282321a0. [DOI] [PubMed] [Google Scholar]
  7. Freudenthal P. S., Steinman R. M. The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7698–7702. doi: 10.1073/pnas.87.19.7698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Havenith C. E., Breedijk A. J., Betjes M. G., Calame W., Beelen R. H., Hoefsmit E. C. T cell priming in situ by intratracheally instilled antigen-pulsed dendritic cells. Am J Respir Cell Mol Biol. 1993 Mar;8(3):319–324. doi: 10.1165/ajrcmb/8.3.319. [DOI] [PubMed] [Google Scholar]
  9. Holt P. G., Oliver J., Bilyk N., McMenamin C., McMenamin P. G., Kraal G., Thepen T. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med. 1993 Feb 1;177(2):397–407. doi: 10.1084/jem.177.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Inaba K., Metlay J. P., Crowley M. T., Steinman R. M. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med. 1990 Aug 1;172(2):631–640. doi: 10.1084/jem.172.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Katz S. I., Tamaki K., Sachs D. H. Epidermal Langerhans cells are derived from cells originating in bone marrow. Nature. 1979 Nov 15;282(5736):324–326. doi: 10.1038/282324a0. [DOI] [PubMed] [Google Scholar]
  12. Larsen C. P., Morris P. J., Austyn J. M. Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection. J Exp Med. 1990 Jan 1;171(1):307–314. doi: 10.1084/jem.171.1.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Liu L. M., MacPherson G. G. Antigen acquisition by dendritic cells: intestinal dendritic cells acquire antigen administered orally and can prime naive T cells in vivo. J Exp Med. 1993 May 1;177(5):1299–1307. doi: 10.1084/jem.177.5.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Metlay J. P., Witmer-Pack M. D., Agger R., Crowley M. T., Lawless D., Steinman R. M. The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies. J Exp Med. 1990 May 1;171(5):1753–1771. doi: 10.1084/jem.171.5.1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nabavi N., Freeman G. J., Gault A., Godfrey D., Nadler L. M., Glimcher L. H. Signalling through the MHC class II cytoplasmic domain is required for antigen presentation and induces B7 expression. Nature. 1992 Nov 19;360(6401):266–268. doi: 10.1038/360266a0. [DOI] [PubMed] [Google Scholar]
  16. O'Doherty U., Steinman R. M., Peng M., Cameron P. U., Gezelter S., Kopeloff I., Swiggard W. J., Pope M., Bhardwaj N. Dendritic cells freshly isolated from human blood express CD4 and mature into typical immunostimulatory dendritic cells after culture in monocyte-conditioned medium. J Exp Med. 1993 Sep 1;178(3):1067–1076. doi: 10.1084/jem.178.3.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ranheim E. A., Kipps T. J. Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal. J Exp Med. 1993 Apr 1;177(4):925–935. doi: 10.1084/jem.177.4.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Romani N., Lenz A., Glassel H., Stössel H., Stanzl U., Majdic O., Fritsch P., Schuler G. Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. J Invest Dermatol. 1989 Nov;93(5):600–609. doi: 10.1111/1523-1747.ep12319727. [DOI] [PubMed] [Google Scholar]
  20. Scheinberg D. A., Tanimoto M., McKenzie S., Strife A., Old L. J., Clarkson B. D. Monoclonal antibody M195: a diagnostic marker for acute myelogenous leukemia. Leukemia. 1989 Jun;3(6):440–445. [PubMed] [Google Scholar]
  21. Schuler G., Steinman R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. doi: 10.1084/jem.161.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Steinman R. M., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med. 1973 May 1;137(5):1142–1162. doi: 10.1084/jem.137.5.1142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Steinman R. M., Lustig D. S., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. 3. Functional properties in vivo. J Exp Med. 1974 Jun 1;139(6):1431–1445. doi: 10.1084/jem.139.6.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Thomas R., Davis L. S., Lipsky P. E. Isolation and characterization of human peripheral blood dendritic cells. J Immunol. 1993 Feb 1;150(3):821–834. [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Young J. W., Koulova L., Soergel S. A., Clark E. A., Steinman R. M., Dupont B. The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro. J Clin Invest. 1992 Jul;90(1):229–237. doi: 10.1172/JCI115840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Young J. W., Steinman R. M. Dendritic cells stimulate primary human cytolytic lymphocyte responses in the absence of CD4+ helper T cells. J Exp Med. 1990 Apr 1;171(4):1315–1332. doi: 10.1084/jem.171.4.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]

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