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Dendritic Cells in Old Age

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Part of the book series: Methods in Molecular Medicine ((MIMM,volume 38))

Abstract

Dendritic cells (DCs) are powerful antigen-presenting cells that have the unique capacity to stimulate naive T-cells (1, 2). DCs are identified by a triad of criteria: Morphologically, they exhibit pronounced cytoplasmic veils that are mobile and can easily be observed under a phase-contrast microscope. These veils become apparent only in the mature state. Phenotypically, they express high levels of major histocompatibility class (MHC) (class I and II), adhesion (CD11c, CD54, CD58), and costimulatory (CD80, CD86, CD40) molecules on their cell surfaces. They also express CD1a and CD83, but lack CD14. On cytocentrifuge smears stained with anti-CD68, a marker of the endocytic system that is abundant in macrophages, DCs display spotlike staining whereas typical macrophages are strongly positive all over the cytoplasm. When looking at forward/side scatter profiles in the fluorescence-activated cell sorter (FACS), DCs show high light scattering and are outside the typical lymphocyte gate. Functionally, they are potent stimulators of resting T lymphocytes in the allogeneic mixed leukocyte reaction. DCs derived from various tissues have been shown to undergo a complex maturation process during which their morphology, phenotype, and function change. DCs are derived from bone marrow progenitors and circulate in the blood as immature precursors before they migrate into peripheral tissues, such as the epidermis, heart, lung, liver, gut, thymus, spleen, and lymph nodes. DCs of myeloid as well as of lymphoid origin have been described (35).

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References

  1. Steinman, R. M. (1991) The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9, 271–296.

    Article  PubMed  CAS  Google Scholar 

  2. Hart, D. N. J. (1997) Dendritic cells: unique leukocyte populations which control the primary immune response. Blood 90, 3245–3287.

    PubMed  CAS  Google Scholar 

  3. Süss, G. and Shortman, K. (1996) A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis. J. Exp. Med. 183, 1789–1796.

    Article  PubMed  Google Scholar 

  4. Steinman, R. M., Pack, M., and Inaba, K. (1997) Dendritic cells in the T-cell areas of lymphoid organs. Immunol. Rev. 156, 25–37.

    Article  PubMed  CAS  Google Scholar 

  5. Kronin, V., Vremec, D., Winkel, K., Classon, B. J., Miller, R. G., Mak, T. W., Shortman, K., and Süss, G. (1997) Are CD8+ dendritic cells (DC) veto cells? The role of CD8 on DC in DC development and in the regulation of CD4 and CD8 T cell responses. Int. Immunol. 9, 1061–1064.

    Article  PubMed  CAS  Google Scholar 

  6. Banchereau, J. and Steinman, R. M. (1998) Dendritic cells and the control of immunity. Nature 392, 245–252.

    Article  PubMed  CAS  Google Scholar 

  7. Schuler, G., Thurner, B., and Romani, N. (1997) Dendritic cells: from ignored cells to major players in T-cell mediated immunity. Int. Arch. Allergy Immunol. 112, 317–322.

    Article  PubMed  CAS  Google Scholar 

  8. Stingl, G. and Bergstresser, P. R. (1995) Dendritic cells: a major story unfolds. Immunol. Today 16, 330–333.

    Article  PubMed  CAS  Google Scholar 

  9. Caux, C., Liu, Y. J., and Banchereau, J. (1995) Recent advances in the study of dendritic cells and follicular dendritic cells. Immunol. Today 16, 2–4.

    Article  PubMed  CAS  Google Scholar 

  10. Romani, N., Lenz, A., Glassel, H., Stossel, H., Stanzl, U., Majdic, O., Fritsch, P., and Schuler, G. (1989) Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. J. Invest. Dermatol. 93, 600–609.

    Article  PubMed  CAS  Google Scholar 

  11. O’Doherty, U., Steinman, R. M., Peng, M., Cameron, P. U., Gezelter, S., Kopeloff, I., Swiggard, W. J., Pope, M., and Bhardwaj, N. (1993) 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. 178, 1067–1078.

    Article  PubMed  Google Scholar 

  12. Pavli, P., Hume, D. A., Van de Pol E., and Doe, W. F. (1993) Dendritic cells, the major antigen-presenting cells of the human colonic lamina propria. Immunology 78, 132–141.

    PubMed  CAS  Google Scholar 

  13. Caux, C., Dezutter-Dambuyant, C., Schmitt, D., and Banchereau, J. (1992) GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells. Nature 360, 258–261.

    Article  PubMed  CAS  Google Scholar 

  14. Romani, N., Reider, D., Heuer, M., Ebner, S., Kämpgen, E., Eibl, B., Niederwieser, D., and Schuler, G. (1996) Generation of mature dendritic cells from human blood: an improved method with special regard to clinical applicability. J. Immunol. Methods 196, 137–151.

    Article  PubMed  CAS  Google Scholar 

  15. Bender, A., Sapp, M., Schuler, G., Steinman, R. M., and Bhardwaj, N. (1996) Improved methods for the generation of dendritic cells from nonproliferating progenitor in human blood. J. Immunol. Methods 196, 121–135.

    Article  PubMed  CAS  Google Scholar 

  16. Cella, M., Sallusto, F., and Lanzavecchia, A. (1997) Origin, maturation and antigen presenting function of dendritic cells. Curr. Opin. Immunol. 9, 10–16.

    Article  PubMed  CAS  Google Scholar 

  17. Robinson, S. P., Saraya, K., and Reid, C. D. (1998) Developmental aspects of dendritic cells in vitro and in vivo. Leuk. Lymphoma 29, 477–490.

    Article  PubMed  CAS  Google Scholar 

  18. Romani, N., Bhardwaj, N., Pope, M., Koch, F., Swiggard, W. J., O’Doherty, U., Witmer-Pack, M. D., Hoffman, L., Schuler, G., Inaba, K., and Steinman, R. M. (1997) Dendritic cells, in Weir’s Handbook of Experimental Immunology (Herzenberg, L. A., ed.), Blackwell Science Oxford, Sect. 156.1-156.14.

    Google Scholar 

  19. Reddy, A., Sapp, M., Feldman, M., Subklewe, M., and Bhardwaj, N. (1997) A monocyte conditioned medium is more effective than defined cytokines in mediating the terminal maturation of human dendritic cells. Blood 90, 3640–3646.

    PubMed  CAS  Google Scholar 

  20. Geissmann, F., Prost, C., Monnet, J. P., Dy, M., Brousse, N., and Hermine, O. (1998) Transforming growth factor β1, in the presence of granulocyte/macrophage colonystimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells. J. Exp. Med. 187, 961–966.

    Article  PubMed  CAS  Google Scholar 

  21. Riedl, E., Strobl, H., Majdic, O., and Knapp, W. (1997) TGF-β1 promotes in vitro generation of dendritc cells by protecting progenitor cells from apoptosis. J. Immunol. 158, 1591–1597.

    PubMed  CAS  Google Scholar 

  22. Lynch, D. H., Andreasen, A., Maraskovsky, E., Whitmore, J., Miller, R. E., and Schuh, J. C. L. (1997) Flt ligand induces tumor regression and antitumor immune responses in vivo. Nat. Med. 6, 625–631.

    Article  Google Scholar 

  23. Zhang, Y., Mukaida, N., Wang, J., Harada, A., Akiyama, M., and Matsushima, K. (1997) Induction of dendritic cell differentiation by granulocyte-macrophage colonystimulating factor, stem cell factor, and tumor necrosis factor alpha in vitro from lineage phenotypes-negative c-kit+ murine hematopoietic progenitor cells. Blood 90, 4842–4853.

    PubMed  CAS  Google Scholar 

  24. Haruna, H., Inaba, M., Inaba, K., Taketani, S., Sugiura, K., Fukuba, Y., Doi, H., Toki, J., Tokunaga, R., and Ikehara, S. (1995) Abnormalities of B cells and dendritic cells in SAMP1 mice. Eur. J. Immunol. 25, 1319–1325.

    Article  PubMed  CAS  Google Scholar 

  25. Sprecher, E., Becker, Y., Kraal, G., Hall, E., Harrison, D., and Shutz, L. D. (1990) Effect of aging on epidermal DC populations in C57BL/6J mice. J. Invest. Dermatol. 94, 247–253.

    Article  PubMed  CAS  Google Scholar 

  26. Belsito, D. V., Epstein, S. P., Schultz, J. M., Baer, R. L., and Thorbecke, G. J. (1989) Enhancement by various cytokines or 2-β-mercaptoethanol of Ia antigen expression on Langerhans cells in skin from normal aged and young mice: effect of cyclosporine A. J. Immunol. 143, 1530–1536.

    PubMed  CAS  Google Scholar 

  27. Choi, K. L. and Sauder, D. N. (1987) Epidermal Langerhans cell density and contact sensitivity in young and aged BALB/c mice. Mech. Ageing Dev. 39, 69–79.

    Article  PubMed  CAS  Google Scholar 

  28. Rittman, B. R., Hill, M. W., Rittman, G. A., and MacKenzie, I. C. (1987) Ageassociated changes in Langerhans cells of murine oral epithelium and epidermis. Arch. Oral. Biol. 32, 885–889.

    Article  PubMed  CAS  Google Scholar 

  29. Schwartz, J. L., Weichselbaum, R., and Frim, S. R. (1983) The effect of aging on the density and distribution of oral mucosal Langerhans cells. Exp. Gerontol. 18, 65–71.

    Article  PubMed  CAS  Google Scholar 

  30. Okiji, T., Kosaka, T., Kamal, A. M. M., Kawashima, N., and Suda, H. (1996) Agerelated changes in the immunoreactivity of the monocyte/macrophage system in rat molar pulp. Arch. Oral Biol. 41, 453–460.

    Article  PubMed  CAS  Google Scholar 

  31. Raffaniello, R. D. and Roy, M. (1990) Immunohistological analysis of the immune cells in the normal oral mucosa of aging mice. Gerontology 9, 51–57.

    CAS  Google Scholar 

  32. Koch, F., Trockenbacher, B., Kämpgen, E., Grauer, O., Stössel, H., Livingstone, A. M., Schuler, G., and Romani, N. (1995) Antigen processing in populations of mature murine dendritic cells is caused by subsets of incompletely matured cells. J. Immunol. 155, 93–100.

    PubMed  CAS  Google Scholar 

  33. Komatsubara, S., Cinader, B., and Muramatsu, S. (1996) Functional competence of dendritic cells of ageing C57BL/6 mice. Scand. J. Immunol. 24, 517–525.

    Article  Google Scholar 

  34. Inaba, K. and Steinman, R. M. (1986) Accessory cell-T lymphocyte interactions. Antigen-dependent and-independent clustering. J. Exp. Med. 163, 247–261.

    Article  PubMed  CAS  Google Scholar 

  35. Ingulli, E., Mondino, A., Khoruts, A., and Jenkins, M. K. (1997) In vivo detection of dendritic cell antigen presentation to CD4+ T cells. J. Exp. Med. 185, 2133–2141.

    Article  PubMed  CAS  Google Scholar 

  36. Koch, F., Stanzl, U., Jennewein, P., Janke, K., Heufler, C., Kämpgen, E., Romani, N., and Schuler, G. (1996) High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J. Exp. Med. 184, 741–746.

    Article  PubMed  CAS  Google Scholar 

  37. Kudo, S., Matsuno, K., Ezaki, T., and Ogawa, M. (1997) A novel migration pathway for rat dendritic cells from the blood: hepatic sinusoids-lymph translocation. J. Exp. Med. 185, 777–784.

    Article  PubMed  CAS  Google Scholar 

  38. Weinlich, G., Heine, M., Stössel, H., Zanella, M., Stoitzner, P., Ortner, U., Smolle, J., Koch, F., Sepp, N. T., Schuler, G., and Romani, N. (1998) Entry into afferent lymphatics and maturation in situ of migrating cutaneous dendritic cells. J. Invest. Dermatol. 110, 441–448.

    Article  PubMed  CAS  Google Scholar 

  39. Villadsen, J. H., Langkjer, S. T., Ebbesen, P., and Bjerring, P. (1987) Syngrafting skin among mice of similar and different ages increases the number of Langerhans cells and decreases responsiveness to 1, 4-dinitrofluorobenzene. Compr. Gerontol. 1, 78–79.

    CAS  Google Scholar 

  40. Ortner, U., Inaba, K., Koch, F., Heine, M., Miwa, M., Schuler, G., and Romani, N. (1996) An improved isolation method for murine migratory cutaneous dendritic cells. J. Immunol. Methods 193, 71–79.

    Article  PubMed  CAS  Google Scholar 

  41. Thiers, B. H., Maize, J. C., Spicer, S. S., and Cantor, A. B. (1984) The effect of aging and chronic sun exposure on human Langerhans cell populations. J. Invest. Dermatol. 82(3), 223–226.

    Article  PubMed  CAS  Google Scholar 

  42. Gilchrest, B. A., Murphy, G. F., and Soter, N. A. (1982) Effect of chronological aging on Langerhans cells in the human epidermis. J. Invest. Deramtol. 79, 85–88.

    Article  CAS  Google Scholar 

  43. Steger, M. M., Maczek, C., and Grubeck-Loebenstein, B. (1996) Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals. Clin. Exp. Immunol. 105, 544–550.

    Article  PubMed  CAS  Google Scholar 

  44. Steger, M. M., Maczek, C., and Grubeck-Loebenstein, B. (1997) Peripheral blood dendritic cells reinduce proliferation in in vitro aged T cell populations. Mech. Ageing Dev. 93, 125–130.

    Article  PubMed  CAS  Google Scholar 

  45. Henderson, R. A., Watkins, S. C., and Flynn, J. L. (1997) Activation of human dendritic cells following infection with Mycobacterium tuberculosis. J. Immunol. 159, 635–643.

    PubMed  CAS  Google Scholar 

  46. Schnorr, J. J., Xanthakos, S., Keikavoussi, P., Kämpgen, E., ter Meulen, V., and Schneider-Schaulies, S. (1997) Induction of maturation of human blood dendritic cell precursors by measles virus is associated with immunosuppression. Proc. Natl. Acad. Sci. USA 94, 5326–5331.

    Article  PubMed  CAS  Google Scholar 

  47. Thurnher, M., Ramoner, R., Gastl, G., Radmayr, C., Böck, G., Herold, M., Klocker, H., and Bartsch, G. (1997) Bacillus Calmette-Guerin mycobacteria stimulate human blood dendritic cells. Int. J. Cancer 70, 128–134.

    Article  PubMed  CAS  Google Scholar 

  48. Romani, N., Heufler C., Koch, F., Kämpgen, E., and Schuler, G. (1999) Dendritic cells as donors and recipients of cytokine signals, in Dendritic Cells: Biology and Clinical Applications (Lotze, M. T. and Thomson, A. W., eds.), Academic Press, London, Sect. 37, 653–672.

    Google Scholar 

  49. Lardon, F., Snoeck, H. W., Berneman, Z. N., Van Tendeloo, V. F., Nijs, G., Lenjou, M., Henckaerts, E., Boeckxtaens, C. J., Vandenabeele, P., Kestens, L. L., Van Bockstaele, D. R., and Vanham, G. L. (1997) Generation of dendritic cells from bone marrow progenitors using GM-CSG, TNF-alpha, and additional cytokines: antagonistic effects of IL-4 and IFN-gamma and selective involvement of TNF-alpha receptor-1. Immunology 91, 553–559.

    Article  PubMed  CAS  Google Scholar 

  50. Saurwein-Teissl, M., Schönitzer, D., and Grubeck-Loebenstein, B. (1998) Dendritic cell responsiveness to stimulation with influenza vaccine is unimpaired in old age. Exp. Gerontol. 33, 625–631.

    Article  PubMed  CAS  Google Scholar 

  51. Schuler, G., Lutz, M. B., Bender, A., Röder, C., and Romani, N. (1999) A guide to the isolation and propagation of dendritic cells, in Dendritic Cells: Biology and Clinical Applications (Lotze M. T. and Thomson, A. W., eds.), Adcademic Press, London, Sect. 27, 515–533.

    Google Scholar 

  52. Koch, F., Kämpgen, E., Schuler, G., and Romani, N (1999) Isolation, enrichment and culture of murine epidermal Langerhans cells, in Dendritic Cell Protocols —Methods in Molecular Medicine (Robinson, S. and Stagg, A. J., eds.), Humana Press, Totowa, NJ, in press.

    Google Scholar 

  53. Inaba, K., Swiggard, W. J., Steinman, R. M., Romani, N., and Schuler, G. (1998) Isolation of dendritic cells, in Current Protocols in Immunology (Coligan, J. E., Kruisbeek, A. M., Margulies, D. H., Shevach, E. M., and Strober, W., eds.), John Wiley & Sons, New York, Sect. 3.7.1-3.7.15.

    Google Scholar 

  54. Rieser, C., Böck, G., Klocker, H., Bartsch, G., and Thurnher, M. (1997) Prostaglandin E2 and tumor necrosis factor α cooperate to activate human dendritic cells: synergistic activation of interleukin 12 production. J. Exp. Med. 196, 1603–1608.

    Article  Google Scholar 

  55. Jonuleit, H., Kühn, U., Müller, G., Steinbrink, K., Paragnik, L., Schmitt, E., Knop, J., and Enk, A. H. (1997) Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur. J. Immunol. 27, 3135–3142.

    Article  PubMed  CAS  Google Scholar 

  56. Schuler, G. and Steinman, R. M. (1985) Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J. Exp. Med. 161, 526–546.

    Article  PubMed  CAS  Google Scholar 

  57. Kämpgen, E., Koch, N., Koch, F., Stoger, P., Heufler, C., Schuler, G., and 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, 3014–3018.

    Article  PubMed  Google Scholar 

  58. Pope, M., Betjes, M. G. H., Hirmand, H., Hoffman, L, and Steinman, R. M. (1995) Both dendritic cells and memory T lymphocytes emigrate from organ cultures of human skin and form distinctive dendritic-T-cell conjugates. J. Invest. Dermatol. 104, 11–17.

    Article  PubMed  CAS  Google Scholar 

  59. Romani, N., Gruner, S., and Brang, D. (1994) Proliferating dendritic cells progenitors in human blood. J. Exp. Med. 180, 83–93.

    Article  PubMed  CAS  Google Scholar 

  60. Inaba, K., Inaba, M., Deguchi, M., Hagi, K., Yasumizu, R., Ikehara, S., Muramatsu, S., and Steinman, R. M. (1993) Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. Proc. Natl. Acad. Sci. USA 90, 3038–3042.

    Article  PubMed  CAS  Google Scholar 

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Grubeck-Loebenstein, B., Saurwein-Teissl, M., Romani, N. (2000). Dendritic Cells in Old Age. In: Barnett, Y.A., Barnett, C.R. (eds) Aging Methods and Protocols. Methods in Molecular Medicine, vol 38. Humana Press. https://doi.org/10.1385/1-59259-070-5:291

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  • DOI: https://doi.org/10.1385/1-59259-070-5:291

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-582-9

  • Online ISBN: 978-1-59259-070-4

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