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The immunologic properties of epidermal Langerhans cells as a part of the dendritic cell system

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Summary

Dendritic cells form a system of antigen-presenting cells that is widely distributed in the body. They constitute trace populations in lymphoid and nonlymphoid tissues and in the circulation. They are characterized by their typical dendritic and “veiled” morphology, by their constitutive expression of high levels of major histocompatibility complex class II molecules on their surface, and by their outstanding capacity to initiate primary immune responses. Dendritic cells occur in two states of differentiation. In the immature state they are highly specialized for processing foreign protein antigens; in the mature state they efficiently stimulate resting antigen-specific T cells. Dendritic cells can migrate from the non-lymphoid tissues, where they reside in the immature state, via the afferent lymphatics or the blood to the T cell-dependent areas of the lymphoid organs (lymph nodes, spleen). There, they appear as mature dendritic cells. Therefore, dendritic cells are ideally suited to mediate important aspects of immunogenicity: they can acquire antigens in the tissues and process them in an immunogenic form; they can carry the immunogen to the lymphoid organs; and they can find and efficiently activate antigen-specific T cell clones and thus generate an immune response. Studies of epidermal Langerhans cells have greatly helped in establishing this concept. They can be investigated freshly isolated from the epidermis where they represent immature (tissue) dendritic cells. After 2–3 days in culture they develop into mature dendritic cells. The mechanisms of dendritic cell maturation, which can be studied best using epidermal Langerhans cells, and the specific functions of Langerhans cells in immunogenicity are discussed.

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References

  1. Aiba S, Katz SI (1991) The ability of cultured Langerhans cells to process and present protein antigens is MHC dependent. J Imunol 146: 2479

    Google Scholar 

  2. Barker CF, Billingham RE (1968) The role of afferent lymphatics in the rejection of skin homografts. J Exp Med 128: 197

    Google Scholar 

  3. Becker D, Reske-Kunz AB, Knop J, Reske K (1991) Biochemical properties of MHC class II molecules endogenously synthesized and expressed by mouse Langerhans cells. Eur J Immunol 21: 1213

    Google Scholar 

  4. Bergstresser PR, Toews GB, Streilein JW (1980) Natural and perturbed distributions of Langerhans cells: responses to ultraviolet light, heterotopic skin grafting, and dinitrofluorobenzene sensitization. J Invest Dermatol 75: 73

    Google Scholar 

  5. Botham PA, Rattray NJ, Walsh ST, Riley EJ (1987) Control of the immune response to contact sensitizing chemicals by cutaneous antigen-presenting cells. Br J Dermatol 117: 1

    Google Scholar 

  6. Breathnach SM (1991) Origin, cell lineage, ontogeny, tissue distribution, and kinetics of Langerhans cells. In: Schuler G (ed) Epidermal Langerhans cells. CRC Press, Boca Raton, pp 23–47

    Google Scholar 

  7. Brodsky FM, Guagliardi LE (1991) The cell biology of antigen processing and presentation. Annu Rev Immunol 9: 707

    Google Scholar 

  8. Bujdoso R, Hopkins J, Dutia BM, Young P, McConnell I (1989) Characterization of sheep afferent lymph dendritic cells and their role in antigen carriage. J Exp Med 170: 1285

    Google Scholar 

  9. Crowley M, Inaba K, Witmer-Pack M, Steinman RM (1989) The cell surface of mouse dendritic cells: FACS analyses of dendritic cells from different tissues including thymus. Cell Immunol 118: 108

    Google Scholar 

  10. Crowley M, Inaba K, Steinman RM (1990) Dendritic cells are the principal cell in mouse spleen bearing immunogenic fragments of foreign proteins. J Exp Med 172: 383

    Google Scholar 

  11. Crowley MT, Inaba K, Witmer-Pack M, Gezelter S, Steinman RM (1990) Use of the fluorescence-activated cell sorter to enrich dendritic cells from mouse spleen. J Immunol Methods 133: 55

    Google Scholar 

  12. Demotz S, Grey HM, Sette A (1990) The minimal number of class II MHC-antigen complexes needed for T cell activation. Science 249: 1028

    Google Scholar 

  13. Faustman DL, Steinman RM, Gebel HM, Hauptfeld V, Davie JM, Lacy PE (1984) Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. Proc Natl Acad Sci USA 81: 3864

    Google Scholar 

  14. Freudenthal PS, Steinman RM (1990) The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci USA 87: 7698

    Google Scholar 

  15. Frey JR, Wenk P (1957) Experimental studies on the pathogenesis of contac eczema in the guinea pig. Int Arch Allergy Appl Immunol 11: 81

    Google Scholar 

  16. Germain RN (1991) Antigen presentation. The second class story. Nature 353: 605

    Google Scholar 

  17. Girolomoni G, Simon JC, Bergstresser PR, Cruz PD Jr (1990) Freshly isolated spleen dendritic cells and epidermal Langerhans cells undergo similar phenotypic and functional changes during short term culture. J Immunol 145: 2820

    Google Scholar 

  18. Hart DNJ, McKenzie JL (1986) Isolation and characterization of human tonsil dendritic cells. J Exp Med 168: 157

    Google Scholar 

  19. Hauser C (1990) Cultured epidermal Langerhans cells activate effector cells for contact sensitivity. J Invest Dermatol 95: 436

    Google Scholar 

  20. Hauser C, Katz SI (1988) Activation and expansion of hapten- and protein-specific T helper cells from nonsensitized mice. Proc Natl Acad Sci USA 85: 5625

    Google Scholar 

  21. Heufler C, Koch F, Schuler G (1987) Granulocyte-macrophage colony-stimulating factor and interleukin-1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med 167: 700

    Google Scholar 

  22. Hoefsmit ECM, Duijvestijn AM, Kamperdijk WA (1982) Relation between Langerhans cells, veiled cells, and interdigitating cells. Immunobiology 161: 255

    Google Scholar 

  23. Inaba K, Steinman RM (1986) Accessory cell — T lymphocyte interactions: antigen dependent and independent clustering. J Exp Med 163: 247

    Google Scholar 

  24. Inaba K, Schuler G, Witmer MD, Valinsky J, Atassi B, Steinman RM (1986) The immunologic properties of purified Langerhans cells: distinct requirements for the stimulation of unprimed and sensitized T lymphocytes. J Exp Med 164: 605

    Google Scholar 

  25. Inaba K, Romani N, Steinman RM (1989) An antigen-independent contact mechanism as an early step in T-cell proliferative responses to dendritic cell. J Exp Med 170: 527

    Google Scholar 

  26. Inaba K, Metlay JP, Crowley MT, Steinman RM (1990) Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med 172: 631

    Google Scholar 

  27. Kämpgen E, Koch N, Koch F, Stöger P, Heufler C, Schuler G, Romani N (1991) 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 88: 3014

    Google Scholar 

  28. Kaplan G, Nusrat A, Witmer MD, Nath I, Cohn ZA (1987) Distribution and turnover of Langerhans cells during delayed immune responses in human skin. J Exp Med 165: 763

    Google Scholar 

  29. King PD, Katz DR (1989) Human tonsillar dendritic cell-induced T-cell responses: analysis of molecular mechanisms using monoclonal antibodies. Eur J Immunol 19: 581

    Google Scholar 

  30. Koch F, Heufler C, Kämpgen E, Schneeweiss D, Böck G, Schuler G (1990) Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture but in contrast to granulocyte/macrophage colony-stimulating factor, does not induce their functional maturation. J Exp Med 171: 159

    Google Scholar 

  31. Kraal G, Breel M, Janse M, Bruin G (1986) Langerhans cells, veiled cells, and interdigitating cells in the mouse recognized by a monoclonal antibody. J Exp Med 163: 981

    Google Scholar 

  32. Kripke ML, Munn CG, Jeevan A, Tang J-M, Bucana C (1990) Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitization. J Immunol 145: 2833

    Google Scholar 

  33. Larsen CP, Morris PJ, Austyn JM (1990) Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection. J Exp Med 171: 307

    Google Scholar 

  34. Larsen CP, Steinman RM, Witmer-Pack M, Hankins DF, Morris PJ, Austyn JM (1990) Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med 172: 1483

    Google Scholar 

  35. Lenz A, Larsen CP, Austyn JM, Fritsch P, Romani N, Schuler G (1990) Human dermal dendritic cells: characterization by means of a novel isolation method (abstract). Arch Dermatol Res 283: 21

    Google Scholar 

  36. Macatonia SE, Knight SC, Edwards AJ, Griffiths S, Fryer P (1987) Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. J Exp Med 166: 1654

    Google Scholar 

  37. MacPherson GG (ed) (1989) Lymphoid dendritic cells: their life history and roles in immune responses. 28th Forum in Immunology. Res Immunol 140: 877

  38. Will A, Blank C, Röllinghof M, Moll H (1992) Murine epidermal Langerhans cells are potent stimulators of an antigen-specific T cell response to Leishmania major, the cause of cutaneous leishmaniasis. Eur J Immunol 22: 1341

    Google Scholar 

  39. Okamoto H, Kripke ML (1987) Effector and suppressor circuits of the immune response are activated in vivo by different mechanisms. Proc Natl Acad Sci USA 84: 3841

    Google Scholar 

  40. Pollard AM, Lipscomp MF (1990) Characterization of murine lung dendritic cells: similarities to Langerhans cells and thymic dendritic cells. J Exp Med 172: 159

    Google Scholar 

  41. Poulter LW, Campbell DA, Munro C, Janossy G (1986) Discrimination of human macrophages and dendritic cells by means of monoclonal antibodies. Scand J Immunol 24: 351

    Google Scholar 

  42. Pugh CW, MacPherson GG, Steer HW (1983) Characterization of non-lymphoid cells derived from rat peripheral lymph. J Exp Med 157: 1758

    Google Scholar 

  43. Puré E, Inaba K, Crowley MT, Tardelli L, Witmer-Pack MD, Ruberti G, Fathman CG, Steinman RM (1990) Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of MHC class II molecules and expression of invariant chain. J Exp Med 172: 1459

    Google Scholar 

  44. Romani N, Inaba K, Witmer-Pack M, Crowley M, Puré E, Steinman RM (1989) A small number of anti-CD3 molecules on dendritic cells stimulate DNA synthesis in mouse T lymphocytes. J Exp Med 169: 1153

    Google Scholar 

  45. Romani N, Koide S, Crowley M, Witmer-Pack M, Livingstone AM, Fathman CG, Inaba K, Steinman RM (1989) 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 169: 1169

    Google Scholar 

  46. Romani N, Lenz A, Glassl H, Stössel H, Stanzl U, Majdic O, Fritsch P, Schuler G (1989) Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. J Invest Dermatol 93: 600

    Google Scholar 

  47. Romani N, Schuler G, Fritsch P (1991) Identification and phenotype of epidermal Langerhans cells. In: Schuler G (ed) Epidermal Langerhans cells. CRC Press, Boca Raton, pp 49–86

    Google Scholar 

  48. Romani N, Witmer-Pack M, Crowley M, Koide S, Schuler G, Inaba K, Steinman RM (1991) Langerhans cells as immature dendritic cells. In: Schuler G (ed) Epidermal Langerhans cells. CRC Press, Boca Raton, pp 191–216

    Google Scholar 

  49. Rudensky AY, Preston-Hurlburt P, Hong S-C, Barlow A, Janeway CA Jr (1991) Sequence analysis of peptides bound to MHC class II molecules. Nature 353: 622

    Google Scholar 

  50. Schon-Hegrad MA, Oliver J, McMenamin PG, Holt PG (1991) Studies on the density, distribution, and surface phenotype of intraepithelial class II major histocompatibility complex antigen (Ia)-bearing dendritic cells (DC) in the conducting airways. J Exp Med 173: 1345

    Google Scholar 

  51. Schuler G (ed) (1991) Epidermal Langerhans cells. CRC Press, Boca Raton

    Google Scholar 

  52. Schuler G, Steinman RM (1985) Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med 161: 526

    Google Scholar 

  53. Schuler G, Romani N, Stössel H, Wolff K (1991) Structural organization and biological properties of epidermal Langerhans cells. In: Schuler G (ed) Epidermal Langerhans cells. CRC Press, Boca Raton, pp 87–137

    Google Scholar 

  54. Shimada S, Caughman SW, Sharrow SO, Stephany D, Katz SI (1987) Enhanced antigen-presenting capacity of cultured Langerhans cells is associated with markedly increased expression of Ia antigen. J Immunol 139: 2551

    Google Scholar 

  55. Silberberg IR, Baer L, Rosenthal SA (1976) The role of Langerhans cells in allergic contact hypersensitivity. A review of findings in man and guinea pigs. J Invest Dermatol 66: 210

    Google Scholar 

  56. Simon JC, Tigelaar RE, Bergstresser PR, Edelbaum D, Cruz PD Jr (1991) Ultraviolet radiation converts Langerhans cells from immunogenic to tolerogenic antigen-presenting cells. Induction of specific clonal anergy in CD4+ T helper 1 cells. J Immunol 146: 485

    Google Scholar 

  57. Simon JC, Edelbaum D, Cruz PD Jr, Kapp A, Krutmann J, Schöpf E, Bergstresser PR (1992) Tumor necrosis factor-alpha (TNF: alpha) distorts the antigen-presenting function of epidermal Langerhans cells (abstract). Arch Dermatol Res 284: 69

    Google Scholar 

  58. Steinman RM (ed) (1990) Dendritic cells. Int Rev Immunol 6: 89

  59. Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9: 271

    Google Scholar 

  60. Steinman RM, Cohn ZA (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137: 1142

    Google Scholar 

  61. Stingl G., Shevach EM (1991) Langerhans cells as antigen presenting cells. In: Schuler G (ed) Epidermal Langerhans cells. CRC Press, Boca Raton, pp 159–190

    Google Scholar 

  62. Stingl G, Katz SI, Clements L, Green I, Shevach EM (1978) Immunologic functions of Ia-bearing epidermal Langerhans cells. J Immunol 121: 2005

    Google Scholar 

  63. Stössel H, Koch F, Kämpgen E, Stöger P, Lenz A, Heufler C, Romani N, Schuler G (1990) Disappearance of certain acidic organelles (endosomes and Langerhans cell granules) accompanies loss of antigen-processing capacity upon culture of epidermal Langerhans cells. J Exp Med 172: 1471

    Google Scholar 

  64. Streilein JW (1989) Antigen-presenting cells in the induction of contact hypersensitivity in mice: evidence that Langerhans cells are sufficient but not required. J Invest Dermatol 93: 443

    Google Scholar 

  65. Streilein JW, Grammer SF, Yoshikawa T, Demidem A, Vermeer M (1990) Functional dichotomy between Langerhans cells that present antigen to naive and to memory/effector T lymphocytes. Immunol Rev 117: 159

    Google Scholar 

  66. Sullivan S, Bergstresser PR, Tigelaar RE, Streilein JW (1986) Induction and regulation of contact hypersensitivity by resident bone marrow-derived, dendritic epidermal cells: Langerhans cells and Thy-1+ epidermal cells. J Immunol 137: 2460

    Google Scholar 

  67. Tang A, Udey MC (1991) Inhibition of epidermal Langerhans cell function by low-dose ultraviolet B radiation. Ultraviolet B radiation selectively modulates ICAM-1 (CD45) expressison by murine Langerhans cells. J Immunol 146: 3347

    Google Scholar 

  68. Teunissen MBM, Wormmeester J, Krieg SR, Peters PJ, Vogels IMC, Kapsenberg ML, Bos JD (1990) Human epidermal Langerhans cells undergo profound morphological changes during in vitro culture. J Invest Dermatol 94: 166

    Google Scholar 

  69. Toews GB, Bergstresser PR, Tigelaar RE, Streilein JW (1980) Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB. J Immunol 124: 445

    Google Scholar 

  70. Tse Y, Cooper KD (1990) Cutaneous dermal Ia+ cells are capable of initiating delayed-type hypersensitivity responses. J Invest Dermatol 94: 267

    Google Scholar 

  71. Weinlich G, Sepp N, Koch F, Schuler G, Romani N (1990) Evidence that Langerhans cells rapidly disappear from the epidermis in response to contact sensitizers but not to tolerogens/nonsensitizers (abstract). Arch Dermatol Res 281: 556

    Google Scholar 

  72. Witmer MD, Steinman RM (1984) The anatomy of peripheral lymphoid organs with emphasis on accessory cells: light microscopic, immunocytochemical studies of mouse spleen, lymph node and Peyer's patch. Am J Anat 170: 465

    Google Scholar 

  73. Witmer-Pack MD, Olivier W, Valinsky J, Schuler G, Steinman RM (1987) Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells. J Exp Med 166: 1484

    Google Scholar 

  74. Witmer-Pack MD, Valinsky J, Olivier W, Steinman RM (1988) Quantitation of surface antigens on cultured murine epidermal Langerhans cells: rapid and selective increase in the level of surface MHC products. J Invest Dermatol 90: 387

    Google Scholar 

  75. Wolff K (1991) The fascinating story that beganin 1868. In: Schuler G (ed) Epidermal Langerhans Cells. CRC Press, Boca Raton, pp 1–21

    Google Scholar 

  76. Young JW, Steinman RM (1988) Accessory cell requirements for the mixed leukocyte reaction and polyclonal mitogens, as studied with a new technique for enriching blood dendritic cells. Cell Immunol 111: 167

    Google Scholar 

  77. Young JW, Koulova L, Soergel SA, Clark EA, Steinman RM, Dopont B (1992) 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 90 (in press)

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Romani, N., Schuler, G. The immunologic properties of epidermal Langerhans cells as a part of the dendritic cell system. Springer Semin Immunopathol 13, 265–279 (1992). https://doi.org/10.1007/BF00200527

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