Advertisement

Murine Epidermal Langerhans Cells as A Model to Study Tissue Dendritic Cells

  • Gerold Schuler
  • Franz Koch
  • Christine Heufler
  • Eckhart Kämpgen
  • Gerda Topar
  • Nikolaus Romani
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 329)

Abstract

Dendritic cells (DC) form a system of widely distributed antigen presenting cells that seems essential to initiate immmune responses 1. The study of epidermal Langerhans cells (LC) was important to unravel how the individual components of this system interact 2. It became evident that DC accomplish their task as “nature’s adjuvant” in the afferent limb of the immune system in three discrete steps: immature DC are located in peripheral non-lymphoid tissues (“tissue DC”) and are specialized to capture and process antigen (“sentinel function”). Following rapid downregulation of their antigen processing capacity they begin to develop into mature DC by acquiring the capacity to stimulate resting T cells. These cells then migrate as “veiled cells” via afferent lymph (or blood) to the T areas of the lymph node (or spleen) (“migratory function”), where they appear as “lymphoid DC”, select antigen-specific T cells from the circulating pool and stimulate them (“sensitizing function”). Here we will review the studies of murine LC that have helped to establish this concept of DC function. We will also outline recent data about the modulation of LC function by cytokines, the evidence that DC and LC constitute a distinct hematopoietic lineage, and hints for a novel role of LC as regulators of keratinocyte proliferation.

Keywords

Mature Dendritic Cell Dendritic Cell Function Stem Cell Inhibitor Lymphoid Dendritic Cell Cytokine Gene Expression Profile 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    R.M. Steinman, The dendritic cell system and its role in immunogenicity, Ann. Rev. Immunol. 7: 371 (1989).CrossRefGoogle Scholar
  2. 2.
    G. Schuler. “Epidermal Langerhans Cells”, CRC Press,Inc., Boca Raton (1991).Google Scholar
  3. 3.
    G. Schuler and R.M. Steinman, Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro, J. Exp. Med. 161: 526 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    K. Inaba, G. Schuler, M.D. Witmer, J. Valinski, B. Atassi, and R.M. Steinman, Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes, J. Exp. Med. 164: 605–613 (1986).PubMedCrossRefGoogle Scholar
  5. 5.
    N. Romani, K. Inaba, E. Pure, M. Crowley, M. Witmer-Pack, and R.M. Steinman, A small number of anti-CD3 molecules on dendritic cells stimulates DNA synthesis in mouse T lymphocytes, J. Exp. Med. 169: 1153 (1989).PubMedCrossRefGoogle Scholar
  6. 6.
    K. Inaba, N. Romani, and R.M. Steinman, An antigen-independent contact mechanism as an early step in T cell-proliferative reponses to dendritic cells, J. Exp. Med. 170: 527 (1989).PubMedCrossRefGoogle Scholar
  7. 7.
    N. Romani, S. Koide, M. Crowley, M. Witmer-Pack, A.M. Livingstone, C.G. Fathman, K. Inaba, and R.M. Steinman, 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 (1989).PubMedCrossRefGoogle Scholar
  8. 8.
    J. W. Streilein, and S.F. Grammer, In vitro evidence that Langerhans cells can adopt two functionally distinct forms capable of antigen presentation to T lymphocytes, J. Immunol. 143: 3925 (1989).PubMedGoogle Scholar
  9. 9.
    S. Aiba, and S. I. Katz, The ability of cultured Langerhans cells to process and present antigens is MHC-dependent, J. Immunol. 146: 2479 (1991).PubMedGoogle Scholar
  10. 10.
    E. Pure, K. Inaba, M.T. Crowley, L. Tardelli, M.D. Witmer-Pack, G. Ruberti, G. Fathman, and R.M. Steinman, 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. 172: 1459 (1990).PubMedCrossRefGoogle Scholar
  11. 11.
    E. Kämpgen, N. Koch, F. Koch, P. Stöger, C. Heufler, G. Schuler, and N. Romani, 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 (1991).PubMedCrossRefGoogle Scholar
  12. 12.
    D. Becker, A.B. Reske-Kunz, J. Knop, and K. Reske, Biochemical properties of MHC class II molecules endogenously synthesized and expressed by mouse Langerhans cells, Eur. J. Immunol. 21: 1213 (1991).PubMedCrossRefGoogle Scholar
  13. 13.
    H. Stössel, F. Koch, E. Kämpgen, P. Stöger, A. Lenz, C. Heufler, N. Romani, and G. Schuler, 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 (1990).PubMedCrossRefGoogle Scholar
  14. 14.
    P. G. Holt, J. Oliver, C McMenamin, and M.A. Schon-Hegrad, Studies on the surface phenotype and functions of dendritic cells in parenchymal lung tissue of the rat, Immunology 75: 582 (1992).PubMedGoogle Scholar
  15. 15.
    C.P. Larsen, R.M. Steinman, M. Witmer-Pack, D.F. Hankins, P.J. Morris, and J.M. Austyn, Migration and maturation of Langerhans cells in skin transplants and explants, J. Exp. Med. 172: 1483 (1990).PubMedCrossRefGoogle Scholar
  16. 16.
    K. Inaba, J.P. Metlay, M.T. Crowley, and R.M. Steinman, Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ, J. Exp. Med. 172: 631 (1990).PubMedCrossRefGoogle Scholar
  17. 17.
    M.D. Witmer-Pack, W. Olivier, J. Valinsky, G. Schuler, and R.M. Steinman, Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells, J. Exp. Med. 166: 1484 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    C. Heufler, F. Koch, and G. Schuler, 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 (1988).PubMedCrossRefGoogle Scholar
  19. 19.
    F. Koch, C. Heufler, E. Kämpgen, D. Schneeweiss, G. Böck, and G. Schuler, Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture but in contrast to granulocyte/macrophage colony-stimulating factor without inducing their functional maturation, J. Exp. Med. 171: 159 (1990).PubMedCrossRefGoogle Scholar
  20. 20.
    A.H. Enk and S.I. Katz, Early molecular events in the induction phase of contact sensitivity, Proc. Natl. Acad. Sci. USA 89: 1398 (1992).PubMedCrossRefGoogle Scholar
  21. 21.
    M. Vermeer and J.W. Streilein, Ultraviolet B light-induced alterations in epidermal Langerhans cells are mediated in part by tumor necrosis factor-alpha, Photodermatol. Photoimmunol. Photomed. 7: 258 (1990).PubMedGoogle Scholar
  22. 22.
    K. Inaba, R.M. Steinman, M. Witmer-Pack, H. Aya, M. Inaba, T. Sudo, S. Wolpe, and G. Schuler, Identification of proliferating dendritic cell precursors in mouse blood, J.Exp. Med. 175: 1157 (1992).PubMedCrossRefGoogle Scholar
  23. 23.
    C. Heufler, G. Topar, F. Koch, B. Trockenbacher, E. Kaempgen, N. Romani, and G. Schuler, 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, submitted.Google Scholar
  24. 24.
    G.J. Graham, E.G. Wright, R. Hewick, S.D. Wolpe, N.M. Wilkie, D. Donaldson, S. Lorimore, and I.B. Pragnell, Identification and characterization of an inhibitor of haemopoietic stem cell proliferation, Nature 344: 442 (1990).PubMedCrossRefGoogle Scholar
  25. 25.
    E.K. Parkinson, G.J. Graham, P. Daubersies, J.E. Burns, C. Heufler, M. Plumb, G. Schuler, and I.B. Pragnell, A haematopoietic stem cell inhibitor (SCI/MIP-1alpha) also inhibits clonogenic keratinocyte proliferation, submitted.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Gerold Schuler
    • 1
  • Franz Koch
    • 1
  • Christine Heufler
    • 1
  • Eckhart Kämpgen
    • 1
  • Gerda Topar
    • 1
  • Nikolaus Romani
    • 1
  1. 1.Department of DermatologyUniversity of InnsbruckInnsbruckAustria

Personalised recommendations