Introduction: Cutaneous Dendritic Cells: Distinctive Antigen-Presenting Cells for Experimental Models and Disease States

  • Ralph M. Steinman
  • Kayo Inaba
  • Gerold Schuler
Part of the Medical Intelligence Unit book series (MIU.LANDES)

Abstract

Cutaneous dendritic cells, which include the Langerhans cells (LC) of the epidermis as well as their counterparts in the dermis and cutaneous lymph, have provided a rich area for investigative dermatology and immunology. The important starting points were the findings that LC are bone marrow-derived and have many properties of white blood cells such as binding of immune complexes, expression of major histocompatibility complex (MHC) class II products, and presentation of antigens to T cells. Much of this work is discussed in a compendium, Epidermal Langerhans Cells, edited by Dr. G. Schuler and published by CRC Press, Boca Raton, FL in 1991. Here, Dr. Heidrun Moll assembles an important series of articles that cover the latest, most timely developments.

Keywords

Migration Arthritis Influenza Bacillus Sarcoma 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Schuler G, Steinman RM. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med 1985; 161: 526–46.PubMedCrossRefGoogle Scholar
  2. 2.
    Bhardwaj N, Young JW, Nisanian AJ et al. Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses. J Exp Med 1993; 178: 633–42.PubMedCrossRefGoogle Scholar
  3. 3.
    Puri E, Inaba K, Crowley MT et al. Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain. J Exp Med 1990; 172: 1459–69.CrossRefGoogle Scholar
  4. 4.
    Inaba K, Metlay JP, Crowley MT et al. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med 1990; 172: 631–40.PubMedCrossRefGoogle Scholar
  5. 5.
    Inaba K, Inaba M, Naito M et al. Dendritic cell progenitors phagocytose particulates, including Bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo. J Exp Med 1993; 178: 479–88.PubMedCrossRefGoogle Scholar
  6. 6.
    Witmer-Pack MD, Valinsky J, Olivier W et al. Quantitation of surface antigens on cultured murine epidermal Langerhans cells: rapid and selective increase in the level of surface MHC products. J Invest Dermatol 1988; 90: 387–94.PubMedCrossRefGoogle Scholar
  7. 7.
    Shimada S, Caughman SW, Sharrow SO et al. Enhanced antigen-presenting capacity of cultured Langerhans cells is associated with markedly increased expression of Ia antigen. J Immunol 1987; 139: 2551–5.PubMedGoogle Scholar
  8. 8.
    Kämpgen E, Koch N, Koch F et al. Class II major histocompatibility complex molecules of murine dendritic cells: synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture. Proc Natl Acad Sci USA 1991; 88: 3014–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Scheicher C, Mehlig M, Zecher R et al. Dendritic cells from mouse bone marrow: in vitro differentiation using low doses of recombinant granulocyte-macrophage colony-stimulating factor. J Immunol Meth 1992; 154: 253–64.CrossRefGoogle Scholar
  10. 10.
    Stössel H, Koch F, Kämpgen E et al. Disappearance of certain acidic organelles (endosomes and Langerhans cell granules) accompanies loss of antigen processsing capacity upon culture of epidermal Langerhans cells. J Exp Med 1990; 172: 1471–82.PubMedCrossRefGoogle Scholar
  11. 11.
    Steinman RM, Kaplan G, Witmer MD et al. Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro. J Exp Med 1979; 149: 1–16.PubMedCrossRefGoogle Scholar
  12. 12.
    Girolomoni G, Cruz Jr PD, Bergstresser PR. Internalization and acidification of surface HLA-DR molecules by epidermal Langerhans cells: A paradigm for antigen processing. J Invest Dermatol 1990; 94: 753.PubMedCrossRefGoogle Scholar
  13. 13.
    Kleijmeer MJ, Oorschot VMJ, Geuze HJ. Human resident Langerhans cells display a lysosomal compartment enriched in MHC class II. J Invest Dermatol 1994; 103: 516–23.PubMedCrossRefGoogle Scholar
  14. 14.
    Tulp A, Verwoerd D, Dobberstein B et al. Isolation and characterization of the intracellular MHC class II compartment. Nature 1994; 369: 120–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Amigorena S, Drake JR, Webster P et al. Transient accumulation of new class II MHC molecules in a novel endocytic compartment in B lymphocytes. Nature 1994; 369: 113–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Larsen CP, Steinman RM, Witmer-Pack MD et al. Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med 1990; 172: 1483–93.PubMedCrossRefGoogle Scholar
  17. 17.
    Enk AH, Angeloni VL, Udey MC et al. An essential role for Langerhans cell-derived IL-lß in the induction of primary immune responses in skin. J Immunol 1993; 150: 3698–704.PubMedGoogle Scholar
  18. 18.
    Zaghouani H, Steinman RM, Nonacs R et al. Efficient presentation of a viral T helper epitope expressed in the CDR3 region of a self immunoglobulin molecule. Science 1993; 259: 224–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Sallusto F, Lanzavecchia A. Dendritic cells concentrate antigen in the class II compartment by macropinocytosis. Downregulation by cytokines and bacterial products. J Exp Med 1995; submitted.Google Scholar
  20. 20.
    Reis e Sousa C, Stahl PD, Austyn JM. Phagocytosis of antigens by Langerhans cells in vitro. J Exp Med 1993; 178: 509–19.CrossRefGoogle Scholar
  21. 21.
    Moll H, Fuchs H, Blank C, Röllinghoff M. Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen-specific T cells. Eur J Immunol 1993; 23: 1595–1601.PubMedCrossRefGoogle Scholar
  22. 22.
    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 a. J Exp Med 1994; 179: 1109–18.PubMedCrossRefGoogle Scholar
  23. 23.
    Romani N, Lenz A, Glassel H et al. Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. J Invest Dermatol 1989; 93: 600–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Teunissen MBM, Wormmeester J, Krieg SR et al. Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture. J Invest Dermatol 1990; 94: 166–73.PubMedCrossRefGoogle Scholar
  25. 25.
    Caux C, Vanbervlict B, Massacrier C et al. B70/B7–2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med 1994; 180: 1841–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Inaba K, Witmer-Pack M, Inaba M et al. The tissue distribution of the B7–2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation. J Exp Med 1994; 180: 1849–60.PubMedCrossRefGoogle Scholar
  27. 27.
    Heufler C, Topar G, Koch F et al. Cytokine gene expression in murine epidermal cell suspensions: Interleukin 1 beta and macrophage inflammatory protein 1 alpha are selectively expressed in Langerhans cells but are differentially regulated in culture. J Exp Med 1992; 176: 1221–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Heufler C, Topar G, Wysocka M et al. Dendritic cells are a source of interleukin-12. J Invest Dermatol 1994; 103: 418 (Abstract).Google Scholar
  29. 29.
    Tang A, Amagai M, Granger LG et al. Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin. Nature 1993; 361: 82–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Steinman RM, Hoffman L, Pope M. Maturation and migration of cutaneous dendritic cells. J Invest Dermatol 1995; in press.Google Scholar
  31. 31.
    Austyn JM, Kupiec-Weglinski JW, Hankins DF et al. Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and binding within marginal zone. J Exp Med 1988; 167: 646–51.PubMedCrossRefGoogle Scholar
  32. 32.
    Fossum S. Lymph-borne dendritic leukocytes do not recirculate, but enter the lymph node paracortex to become interdigitating cells. Scand J Immunol 1989; 27: 97–105.CrossRefGoogle Scholar
  33. 33.
    Havenith CEG, Breedijk AJ, Betjes MGH et al. T cell priming in situ by intratracheally instilled antigen-pulsed dendritic cells. Am J Resp Cell, and Molec Biol 1993; 8: 319–24.CrossRefGoogle Scholar
  34. 34.
    Liu LM, MacPherson GG. Antigen acquisition by dendritic cells: Intestinal dendritic cells acquire antigen administered orally and can prime naive T cells “in vivo. ” J Exp Med 1993; 177: 1299–1307.PubMedCrossRefGoogle Scholar
  35. 35.
    Sornasse T, Flamand V, DeBecker G et al. Antigen-pulsed dendritic cells can efficiently induce an antibody response in vivo. J Exp Med 1992; 175: 15–21.PubMedCrossRefGoogle Scholar
  36. 36.
    Romani N, Inaba K, Puré E et al. A small number of anti-CD3 molecules on dendritic cells stimulate DNA synthesis in mouse T lymphocytes. J Exp Med 1989; 169: 1153–68.PubMedCrossRefGoogle Scholar
  37. 37.
    Romani N, Koide S, Crowley M et al. 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; 169: 1169–78.PubMedCrossRefGoogle Scholar
  38. 38.
    Streilein JW, Grammer SF. In vitro evidence that Langerhans cells can adopt two functionally distinct forms capable of antigen presentation to T lymphocytes. J Immunol 1989; 143: 3925–33.PubMedGoogle Scholar
  39. 39.
    Larsen CP, Ritchie SC, Hendrix R et al. Regulation of immunostimulatory function and costimulatory molecule (B7–1 and B7–2) expression on murine dendritic cells. J Immunol 1994; 152: 5208–19.PubMedGoogle Scholar
  40. 40.
    Kämpgen E, Koch F, Heufler C et al. Understanding the dendritic cell lineage through a study of cytokine receptors. J Exp Med 1994; 179: 1767–76.PubMedCrossRefGoogle Scholar
  41. 41.
    Witmer-Pack MD, Olivier W, Valinsky J et al. Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells. J Exp Med 1987; 166: 1484–98.PubMedCrossRefGoogle Scholar
  42. 42.
    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 1987; 167: 700–5.CrossRefGoogle Scholar
  43. 43.
    Silberberg-Sinakin I, Thorbecke GJ, Baer RL et al. Antigen-bearing Langerhans cells in skin, dermal lymphatics and in lymph nodes. Cell Immunol 1976; 25: 137–51.PubMedCrossRefGoogle Scholar
  44. 44.
    Shelley WB, Juhlin L. Langerhans cells form a reticuloepithelial trap for external contact allergens. Nature 1976; 261: 46–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Frey JR, Wenk P. Experimental studies on the pathogenesis of contact eczema in the guinea pig. Intl Arch Allergy Appl Immunol 1957; 11: 81–100.CrossRefGoogle Scholar
  46. 46.
    Weinlich G, Sepp N, Koch F et al. Evidence that Langerhans cells rapidly disappear from the epidermis in response to contact sensitizers but not to tolerogens/ nonsensitizers. Arch Dermatol Res 1989; 281: 556 (Abstract).Google Scholar
  47. 47.
    Roake JA, Rao AS, Morris PJ et al. Dendritic cell loss from non-lymphoid tissues following systemic administration of lipopolysaccharide, tumour necrosis factor, and interleukin-1. Submitted.Google Scholar
  48. 48.
    Larsen CP, Morris PJ, Austyn JM. Migration of dendritic leukocytes from cardiac allografts into host spleens: a novel pathway for initiation of rejection. J Exp Med 1990; 171: 307–14.PubMedCrossRefGoogle Scholar
  49. 49.
    Inaba K, Steinman RM, Witmer-Pack M et al. Identification of proliferating dendritic cell precursors in mouse blood. J Exp Med 1992; 175: 1157–67.PubMedCrossRefGoogle Scholar
  50. 50.
    Cumberbatch M, Kimber I. Dermal tumour necrosis factor-alpha induces dendritic cell migration to draining lymph nodes, and possibly provides one stimulus for Langerhans’ cell migration. Immunology 1992; 75: 257–63.PubMedGoogle Scholar
  51. 51.
    MacPherson GG, Jenkins CD, Stein MJ et al. Endotoxin-mediated dendritic cell release from the intestine: Characterization of released dendritic cells and TNF dependence. J Immunol 1995; in press.Google Scholar
  52. 52.
    Ma J, Wang JH, Guo YJ et al. In vivo treatment with anti-ICAM and anti-LFA-1 antibodies inhibits contact sensitization-induced migration of epidermal Langerhans cells to regional lymph nodes. Cell Immunol 1994; 158: 389–99.PubMedCrossRefGoogle Scholar
  53. 53.
    Pope M, Betjes MGH, Hirmand H et al. Both dendritic cells and memory T lymphocytes emigrate from organ cultures of human skin and form distinctive dendritic-T cell conjugates. J Invest Dermatol 1995; in press.Google Scholar
  54. 54.
    Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol 1994; 12: 991–1045.PubMedCrossRefGoogle Scholar
  55. 55.
    Enk AH, Saloga J, Becker D et al. Induction of hapten-specific tolerance by interleukin-10 in vivo. J Exp Med 1994; 179: 1397–1402.PubMedCrossRefGoogle Scholar
  56. 56.
    Kämpgen E, Koch F, Enk AH et al. TNF alpha as well as IL-10 treated epidermal Langerhans cells induce antigen-specific tolerance yet by distinct mechanisms. Arch Dermatol Res 1995; in press.Google Scholar
  57. 57.
    Bieber T, de la Salle H, Wollenberg A et al. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon). J Exp Med 1992; 175: 1285–90.CrossRefGoogle Scholar
  58. 58.
    Wang B, Rieger A, Kilgus O et al. Epidermal Langerhans cells from normal human skin bind monomeric IgE via Fc epsilon RI. J Exp Med 1992; 175: 1353–65.PubMedCrossRefGoogle Scholar
  59. 59.
    Muller KM, Jaunin F, Masouye I et al. Th2 cells mediate IL-4dependent local tissue inflammation. J Immunol 1993; 150: 5576–84.PubMedGoogle Scholar
  60. 60.
    Lechler RI, Batchelor JR. Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med 1982; 155: 31–41.PubMedCrossRefGoogle Scholar
  61. 61.
    Perreault C, Pelletier M, Belanger R et al. Persistence of host Langerhans cells following allogeneic bone marrow transplantation: possible relationship with acute graft-versus-host disease. Br J Haematol 1985; 60: 253–60.PubMedCrossRefGoogle Scholar
  62. 62.
    Starzl TE, Demetris AJ, Murase N et al. Cell migration, chimer-ism, and graft acceptance. Lancet 1992; 339: 1579–82.PubMedCrossRefGoogle Scholar
  63. 63.
    Bhardwaj N, Bender A, Gonzalez N et al. Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8* T cells. J Clin Invest 1994; 94: 797–807.PubMedCrossRefGoogle Scholar
  64. 64.
    Inaba K, Inaba M, Romani N et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte-macrophage colony stimulating factor. J Exp Med 1992; 176: 1693–1702.PubMedCrossRefGoogle Scholar
  65. 65.
    Caux C, Dezutter-Dambuyant C, Schmitt D et al. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 1992; 360: 258–61.PubMedCrossRefGoogle Scholar
  66. 66.
    Romani N, Gruner S, Brang D et al. Proliferating dendritic cell progenitors in human blood. J Exp Med 1994; 180: 83–93.PubMedCrossRefGoogle Scholar
  67. 67.
    Wood GS, Warner NL, Warnke RA. Anti-Leu-3/T4 antibodies react with cells of monocyte/macrophage and Langerhans lineage. J Immunol 1983; 131: 212–6.PubMedGoogle Scholar
  68. 68.
    Cimarelli A, Zambruno G, Marconi A et al. Quantitation by competitive PCR of HIV-1 proviral DNA in epidermal Langerhans cells of HIV-infected patients. J Acquir Immune Defic Syndr 1994; 7: 230–5.PubMedGoogle Scholar
  69. 69.
    Pope M, Betjes MGH, Romani N et al. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 1994; 78: 389–98.PubMedCrossRefGoogle Scholar
  70. 70.
    Richters CD, Hoekstra MJ, van Baare J et al. Isolation and chracterization of migratory human skin dendritic cells. Clin Exp Immunol 1994; 98: 330–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Foster CA, Yokozeki H, Rappersberger K et al. Human epidermal T cells predominantly belong to the lineage expressing alpha/beta T cell receptor. J Exp Med 1990; 171: 997–1013.PubMedCrossRefGoogle Scholar
  72. 72.
    Mackay CR, Marston WL, Dudler L. Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med 1990; 171: 801–18.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Ralph M. Steinman
  • Kayo Inaba
  • Gerold Schuler

There are no affiliations available

Personalised recommendations