Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Dendritic cells: versatile controllers of the immune system

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Dendritic cells as they are appear in the skin (and other body surfaces).
Figure 2
Figure 3: Phase contrast of a splenic dendritic cell.
Figure 4
Figure 5

References

  1. Banchereau, J. et al. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767–811 (2000).

    Article  CAS  Google Scholar 

  2. Lanzavecchia, A. & Sallusto, F. Regulation of T cell immunity by dendritic cells. Cell 106, 263–266 (2001).

    Article  CAS  Google Scholar 

  3. Moser, M. Dendritic cells in immunity and tolerance—do they display opposite functions? Immunity 19, 5–8 (2003).

    Article  CAS  Google Scholar 

  4. Pulendran, B. Variegation of the immune response with dendritic cells and pathogen recognition receptors. J. Immunol. 174, 2457–2465 (2005).

    Article  CAS  Google Scholar 

  5. Trombetta, E.S. & Mellman, I. Cell biology of antigen processing in vitro and in vivo. Annu. Rev. Immunol. 23, 975–1028 (2005).

    Article  CAS  Google Scholar 

  6. Burnet, F.M. A modification of Jerne's theory of antibody production using the concept of clonal selection. Aust. J. Sci. 20, 67–69 (1957).

    Google Scholar 

  7. Lederberg, J. Genes and antibodies. Science 129, 1649–1653 (1959).

    Article  CAS  Google Scholar 

  8. Brack, C., Hirama, M., Lenhard-Schuller, R. & Tonegawa, S. A complete immunoglobulin gene is created by somatic recombination. Cell 15, 1–14 (1978).

    Article  CAS  Google Scholar 

  9. Nussenzweig, M.C. et al. Allelic exclusion in transgenic mice that express the membrane form of immunoglobulin mu. Science 236, 816–819 (1987).

    Article  CAS  Google Scholar 

  10. Nossal, G.J.V., Abbot, A., Mitchell, J. & Lummus, Z. Antigen in immunity. XV. Ultrastructural features of antigen capture in primary and secondary lymphoid follicles. J. Exp. Med. 127, 277–296 (1968).

    Article  CAS  Google Scholar 

  11. Unanue, E.R. & Cerottini, J.-C. The immunogenicity of antigen bound to the plasma membrane of macrophages. J. Exp. Med. 131, 711–726 (1970).

    Article  CAS  Google Scholar 

  12. Cohn, Z.A. The macrophage—versatile element of inflammation. In The Harvey Lectures 1981–1982, Series 77 63–80 (Academic Press, New York, 1983).

    Google Scholar 

  13. Steinman, R.M. & Cohn, Z.A. The interaction of soluble horseradish peroxidase with mouse peritoneal macrophages in vitro. J. Cell Biol. 55, 186–204 (1972).

    Article  CAS  Google Scholar 

  14. Steinman, R.M. & Cohn, Z.A. The interaction of particulate horseradish peroxidase (HRP)-anti HRP immune complexes with mouse peritoneal macrophages in vitro. J. Cell Biol. 55, 616–634 (1972).

    Article  CAS  Google Scholar 

  15. Mishell, R.I. & Dutton, R.W. Immunization of dissociated spleen cell cultures from normal mice. J. Exp. Med. 126, 423–442 (1967).

    Article  CAS  Google Scholar 

  16. Mosier, D.E. A requirement for two cell types for antibody formation in vitro. Science 158, 1573–1575 (1967).

    Article  CAS  Google Scholar 

  17. 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. 137, 1142–1162 (1973).

    Article  CAS  Google Scholar 

  18. Steinman, R.M. & Cohn, Z.A. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J. Exp. Med. 139, 380–397 (1974).

    Article  CAS  Google Scholar 

  19. Steinman, R.M. & Witmer, M.D. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc. Natl. Acad. Sci. USA 75, 5132–5136 (1978).

    Article  CAS  Google Scholar 

  20. Nussenzweig, M.C., Steinman, R.M., Gutchinov, B. & Cohn, Z.A. Dendritic cells are accessory cells for the development of anti-trinitrophenyl cytotoxic T lymphocytes. J. Exp. Med. 152, 1070–1084 (1980).

    Article  CAS  Google Scholar 

  21. Steinman, R.M., Gutchinov, B., Witmer, M.D. & Nussenzweig, M.C. Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice. J. Exp. Med. 157, 613–627 (1983).

    Article  CAS  Google Scholar 

  22. Van Voorhis, W.C. et al. Relative efficacy of human monocytes and dendritic cells as accessory cells for T cell replication. J. Exp. Med. 158, 174–191 (1983).

    Article  CAS  Google Scholar 

  23. Inaba, K., Steinman, R.M., Van Voorhis, W.C. & Muramatsu, S. Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and man. Proc. Natl. Acad. Sci. USA 80, 6041–6045 (1983).

    Article  CAS  Google Scholar 

  24. Inaba, K. & Steinman, R.M. Protein-specific helper T lymphocyte formation initiated by dendritic cells. Science 229, 475–479 (1985).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  26. Romani, N. 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. 169, 1169–1178 (1989).

    Article  CAS  Google Scholar 

  27. Steinman, R.M. Dendritic cells: from the fabric of immunology. Clin. Invest. Med. 27, 231–236 (2004).

    PubMed  Google Scholar 

  28. Steinman, R.M. Dendritic cells: understanding immunogenicity. Eur. J. Immunol. (in the press).

  29. Zinkernagel, R.M. & Doherty, P.C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248, 701–702 (1974).

    Article  CAS  Google Scholar 

  30. Doherty, P.C. & Zinkernagel, R.M. H-2 compatibility is required for T-cell mediated lysis of target cells infected with lymphocytic choriomeningitis virus. J. Exp. Med. 141, 502–507 (1975).

    Article  CAS  Google Scholar 

  31. Zinkernagel, R.M. On the thymus in the differentiation of “H-2 self-recognition” by T cells: evidence for dual recognition? J. Exp. Med. 147, 882–896 (1978).

    Article  CAS  Google Scholar 

  32. Rescigno, M. et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2, 361–367 (2001).

    Article  CAS  Google Scholar 

  33. Niess, J.H. et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307, 254–258 (2005).

    Article  CAS  Google Scholar 

  34. Chieppa, M., Rescigno, M., Huang, A.Y.C. & Germain, R.N. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp. Med. 203, 2841–2852 (2006).

    Article  CAS  Google Scholar 

  35. Lindquist, R.L. et al. Visualizing dendritic cell networks in vivo. Nat. Immunol. 5, 1243–1250 (2004).

    Article  CAS  Google Scholar 

  36. Bousso, P. & Robey, E. Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes. Nat. Immunol. 4, 579–585 (2003).

    Article  CAS  Google Scholar 

  37. Miller, M.J., Safrina, O., Parker, I. & Cahalan, M.D. Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. J. Exp. Med. 200, 847–856 (2004).

    Article  CAS  Google Scholar 

  38. Castellino, F. et al. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell–dendritic cell interaction. Nature 440, 890–895 (2006).

    Article  CAS  Google Scholar 

  39. Shakhar, G. et al. Stable T cell–dendritic cell interactions precede the development of both tolerance and immunity in vivo. Nat. Immunol. 6, 707–714 (2005).

    Article  CAS  Google Scholar 

  40. Hawiger, D. et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194, 769–780 (2001).

    Article  CAS  Google Scholar 

  41. Bonifaz, L. et al. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J. Exp. Med. 196, 1627–1638 (2002).

    Article  CAS  Google Scholar 

  42. Liu, K. et al. Immune tolerance after delivery of dying cells to dendritic cells in situ. J. Exp. Med. 196, 1091–1097 (2002).

    Article  CAS  Google Scholar 

  43. Badovinac, V.P., Messingham, K.A., Jabbari, A., Haring, J.S. & Harty, J.T. Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination. Nat. Med. 11, 748–756 (2005).

    Article  CAS  Google Scholar 

  44. Zammit, D.J., Cauley, L.S., Pham, Q.M. & Lefrancois, L. Dendritic cells maximize the memory CD8 T cell response to infection. Immunity 22, 561–570 (2005).

    Article  CAS  Google Scholar 

  45. Trumpfheller, C. et al. Intensified and protective CD4+ T cell immunity at a mucosal surface after a single dose of anti-dendritic cell HIV gag fusion antibody vaccine. J. Exp. Med. 203, 607–617 (2006).

    Article  CAS  Google Scholar 

  46. Wang, Y.H. et al. Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity 24, 827–838 (2006).

    Article  CAS  Google Scholar 

  47. Dhodapkar, M.V., Steinman, R.M., Krasovsky, J., Münz, C. & Bhardwaj, N. Antigen specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med. 193, 233–238 (2001).

    Article  CAS  Google Scholar 

  48. Probst, H.C., Lagnel, J., Kollias, G. & van den Broek, M. Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity 18, 713–720 (2003).

    Article  CAS  Google Scholar 

  49. Tarbell, K.V. et al. Dendritic cell–expanded, islet-specific, CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J. Exp. Med. 204, 191–201 (2007).

    Article  CAS  Google Scholar 

  50. Luo, X. et al. Dendritic cells with TGF-β1 differentiate naive CD4+CD25 T cells into islet-protective Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. USA 104, 2821–2826 (2007).

    Article  CAS  Google Scholar 

  51. Iwata, M. et al. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21, 527–538 (2004).

    Article  CAS  Google Scholar 

  52. Coombes, J.L. et al. A functionally specialized population of mucosal CD103+ DCs induce Foxp3+ regulatory T cells via a TGF-β− and retinoic acid–dependent mechanism. J. Exp. Med. 204, 1757–1764 (2007).

    Article  CAS  Google Scholar 

  53. Guermonprez, P., Valladeau, J., Zitvogel, L., Thery, C. & Amigorena, S. Antigen presentation and T cell stimulation by dendritic cells. Annu. Rev. Immunol. 20, 621–667 (2002).

    Article  CAS  Google Scholar 

  54. Soares, H. et al. A subset of dendritic cells induces CD4+ T cells to produce IFN-γ by an IL-12–independent but CD70-dependent mechanism in vivo. J. Exp. Med. 204, 1095–1106 (2007).

    Article  CAS  Google Scholar 

  55. Dudziak, D. et al. Differential antigen processing by dendritic cell subsets in vivo. Science 315, 107–111 (2007).

    Article  CAS  Google Scholar 

  56. Bonifaz, L.C. et al. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J. Exp. Med. 199, 815–824 (2004).

    Article  CAS  Google Scholar 

  57. Bozzacco, L. et al. DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes. Proc. Natl. Acad. Sci. USA 104, 1289–1294 (2007).

    Article  CAS  Google Scholar 

  58. Albert, M.L., Sauter, B. & Bhardwaj, N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392, 86–89 (1998).

    Article  CAS  Google Scholar 

  59. Savina, A. et al. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell 126, 205–218 (2006).

    Article  CAS  Google Scholar 

  60. Reis e Sousa, C. Dendritic cells in a mature age. Nat. Rev. Immunol. 6, 476–483 (2006).

    Article  CAS  Google Scholar 

  61. Münz, C., Steinman, R.M. & Fujii, S. Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity. J. Exp. Med. 202, 203–207 (2005).

    Article  Google Scholar 

  62. Fujii, S., Liu, K., Smith, C., Bonito, A.J. & Steinman, R.M. The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J. Exp. Med. 199, 1607–1618 (2004).

    Article  CAS  Google Scholar 

  63. Del Rio, M.L., Rodriguez-Barbosa, J.I., Kremmer, E. & Forster, R. CD103 and CD103+ bronchial lymph node dendritic cells are specialized in presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells. J. Immunol. 178, 6861–6866 (2007).

    Article  CAS  Google Scholar 

  64. Feldmann, M. & Maini, R.N. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat. Med. 9, 1245–1250 (2003).

    Article  CAS  Google Scholar 

  65. Lowes, M.A. et al. Increase in TNFα and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc. Natl. Acad. Sci. USA 102, 19057–19062 (2005).

    Article  CAS  Google Scholar 

  66. Means, T.K. et al. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J. Clin. Invest. 115, 407–417 (2005).

    Article  CAS  Google Scholar 

  67. Tian, J. et al. Toll-like receptor 9–dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat. Immunol. 8, 487–496 (2007).

    Article  CAS  Google Scholar 

  68. Soumelis, V. et al. Human epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLP. Nat. Immunol. 3, 673–680 (2002).

    Article  CAS  Google Scholar 

  69. Traidl-Hoffmann, C. et al. Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization. J. Exp. Med. 201, 627–636 (2005).

    Article  CAS  Google Scholar 

  70. Boscardin, S.B. et al. Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses. J. Exp. Med. 203, 599–606 (2006).

    Article  CAS  Google Scholar 

  71. Waldmann, T.A. Immunotherapy: past, present and future. Nat. Med. 9, 269–277 (2003).

    Article  CAS  Google Scholar 

  72. Blattman, J.N. & Greenberg, P.D. Cancer immunotherapy: a treatment for the masses. Science 305, 200–205 (2004).

    Article  CAS  Google Scholar 

  73. Palade, G.E. In Les Prix Nobel 1974 (ed. Odelberg, W.) 36–37 (Imprimerie Royale P.A. Norstedt & Söner, Stockholm, 1975)

    Google Scholar 

Download references

Acknowledgements

I thank the jury of the Lasker Awards for selecting dendritic cells for the 2007 Lasker Award in Basic Medical Science. There are so many areas of progress in our profession that I am lucky and honored to work in a subject that has been deemed worthy of recognition by the Lasker Foundation. During my career, I have received help from many quarters. Z. Cohn was my vital mentor and colleague in the demanding early years of dendritic-cell research. The US National Institutes of Health and many foundations generously supported our research. The field of immunology has repeatedly provided the methods, findings and concepts that have been essential for our progress. The community of dendritic-cell biologists has beautifully unraveled the field that is celebrated this year. The Rockefeller University, my professional home for 37 years, has provided inspiring traditions in cell biology, immunology and patient-based research, as well as a fantastic community devoted to science for the benefit of humankind. My colleagues in and out of the lab have been exceptional for their commitment and insights. I am particularly indebted to C. Moberg for editorial help with manuscripts and to my senior colleagues M. Nussenzweig and J. Ravetch for continuing friendship and collaboration. My family has always inspired me with their special dispositions, talents and support.

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The author is a scientific consultant to Celldex, which is developing vaccines based on delivery of antigens to dendritic cells.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Steinman, R. Dendritic cells: versatile controllers of the immune system. Nat Med 13, 1155–1159 (2007). https://doi.org/10.1038/nm1643

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm1643

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing