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.

  • Review Article
  • Published:

Mouse and human dendritic cell subtypes

Nature Reviews Immunology volume 2, pages 151–161 (2002)Cite this article

Key Points

  • The dendritic cell (DC) systems of human and mouse are similar.

  • Many apparent distinctions between human and murine DCs reflect differences in tissue origin and differences between cultured and freshly isolated DCs.

  • Human and mouse DCs can be divided into several subtypes on the basis of surface antigen differences.

  • Many DC subtypes respond differently to microbial products, produce different cytokines and regulate the responses of the T cells they activate.

  • DC subtypes differ in their functional potential but the expression of function is flexible and regulated by environmental factors.

  • Many DC subtypes are products of separate developmental sublineages with different immediate precursors (pDC).

  • DC can be of myeloid or lymphoid origin but this does not determine the DC subtype produced.

  • Some DC sublineages only produce DCs from pDCs in response to microbial products or other danger signals.

  • Some DC subtypes remain in a mature but quiescent state unless activated by microbial products or other danger signals.

  • The dynamics of these shifts in the DC system in response to microbial invasion might determine the balance between tolerance and immunity.

Abstract

Dendritic cells (DCs) collect and process antigens for presentation to T cells, but there are many variations on this basic theme. DCs differ in the regulatory signals they transmit, directing T cells to different types of immune response or to tolerance. Although many DC subtypes arise from separate developmental pathways, their development and function are modulated by exogenous factors. Therefore, we must study the dynamics of the DC network in response to microbial invasion. Despite the difficulty of comparing the DC systems of humans and mice, recent work has revealed much common ground.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Dendritic cells and immunoregulation.
Figure 2: Alternative models for the generation of functionally distinct dendritic cell (DC) subtypes.
Figure 3: CD8+ dendritic cells (DCs) isolated from mouse spleen.
Figure 4: Pathways of human dendritic cell (DC) development.

Similar content being viewed by others

References

  1. Steinman, R. M. The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9, 271–296 (1991).A survey of all the early DC work by the father of the field.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  3. Matzinger, P. Tolerance, danger, and the extended family. Annu. Rev. Immunol. 12, 991–1045 (1994).The danger concept by its main proponent.

    CAS  PubMed  Google Scholar 

  4. Brocker, T., Riedinger, M. & Karjalainen, K. Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative but not positive selection of thymocytes in vivo. J. Exp. Med. 185, 541–550 (1997).The clearest evidence that thymic negative selection is DC mediated.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Matzinger, P. & Guerder, S. Does T-cell tolerance require a dedicated antigen-presenting cell? Nature 338, 74–76 (1989).

    CAS  PubMed  Google Scholar 

  6. Ardavin, C., Wu, L., Li, C. L. & Shortman, K. Thymic dendritic cells and T cells develop simultaneously within the thymus from a common precursor population. Nature 362, 761–763 (1993).First evidence for a lymphoid origin of some DCs.

    CAS  PubMed  Google Scholar 

  7. Heath, W. R. & Carbone, F. R. Cross-presentation, dendritic cells, tolerance and immunity. Annu. Rev. Immunol. 19, 47–64 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Inaba, K. et al. High levels of a major histocompatibility complex II–self peptide complex on dendritic cells from the T cell areas of lymph nodes. J. Exp. Med. 186, 665–672 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Kurts, C., Kosaka, H., Carbone, F. R., Miller, J. F. A. P. & Heath, W. R. Class-I restricted cross-presentation of exogenous self antigen levels to deletion of autoreactive CD8+ T cells. J. Exp. Med. 186, 239–245 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Grohmann, U. et al. IL-6 inhibits the tolerogenic function of CD8α+ dendritic cells expressing indoleamine 2,3-dioxygenase. J. Immunol. 167, 708–714 (2001).

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  12. Fazekas de St Groth, B. F. The evolution of self-tolerance: a new cell arises to meet the challenge of self-reactivity. Immunol. Today 19, 448–454 (1998).

    CAS  PubMed  Google Scholar 

  13. Dhodapkar, M. V., Steinman, R. M., Krasovsky, J., Munz, 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Steinman, R. M., Turley, S., Mellman, I. & Inaba, K. The induction of tolerance by dendritic cells that have captured apoptotic cells. J. Exp. Med. 191, 411–416 (2000).A model of how DCs might mediate self-tolerance.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Roncarolo, M. G., Levings, M. K. & Traversari, C. Differentiation of T regulatory cells by immature dendritic cells. J. Exp. Med. 193, F5–F9 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Albert, M. L., Jegathesan, M. & Darnell, R. B. Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells. Nat Immunol 11, 1010–1017 (2001). | PubMed |A new look at how DCs determine tolerance versus immunity.

    Google Scholar 

  17. Shortman, K. & Heath, W. R. Immunity or tolerance? That is the question for dendritic cells. Nature Immunol. 2, 988–989 (2001).

    CAS  Google Scholar 

  18. Hartmann, G., Weiner, G. J. & Krieg, A. M. CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. Proc. Natl Acad. Sci. USA 96, 9305–9310 (1999).Bacterial DNA as a danger signal for DCs.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Sparwasser, T. et al. Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. Eur. J. Immunol. 28, 2045–2054 (1998).

    CAS  PubMed  Google Scholar 

  20. Verdijk, R. M. et al. Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells. J. Immunol. 163, 57–61 (1999).

    CAS  PubMed  Google Scholar 

  21. Singh-Jasuja, H. et al. The heat shock protein gp96 induces maturation of dendritic cells and downregulation of its receptor. Eur. J. Immunol. 30, 2211–2215 (2000).

    CAS  PubMed  Google Scholar 

  22. Sauter, B. et al. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J. Exp. Med. 191, 423–434 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Gallucci, S., Lolkema, M. & Matzinger, P. Natural adjuvants: endogenous activators of dendritic cells. Nature Med. 5, 1249–1255 (1999).

    CAS  PubMed  Google Scholar 

  24. Medzhitov, R. & Janeway, C., Jr. Innate immune recognition: mechanisms and pathways. Immunol. Rev. 173, 89–97 (2000).Toll and other receptors for microbial products.

    CAS  PubMed  Google Scholar 

  25. Kadowaki, N. et al. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194, 863–870 (2001).A basis for the varied responses of different DC lineages.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Mellman, I. & Steinman, R. M. Dendritic cells: specialized and regulated antigen processing machines. Cell 106, 255–258 (2001).

    CAS  PubMed  Google Scholar 

  27. Villadangos, J. A. Presentation of antigens by MHC class II molecules: getting the most out of them. Mol. Immunol. 38, 329–346 (2001).

    CAS  PubMed  Google Scholar 

  28. Heath, W. & Carbone, F. R. Cross-presentation in viral immunity and self-tolerance. Nature Rev. Immunol. 1, 126–134 (2001).

    CAS  Google Scholar 

  29. Shen, Z., Reznikoff, G., Dranoff, G. & Rock, K. L. Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J. Immunol. 158, 2723–2730 (1997).

    CAS  PubMed  Google Scholar 

  30. 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).

    CAS  PubMed  Google Scholar 

  31. Svensson, M., Stockinger, B. & Wick, M. J. Bone marrow-derived dendritic cells can process bacteria for MHC-I and MHC-II presentation to T cells. J. Immunol. 158, 4229–4236 (1997).

    CAS  PubMed  Google Scholar 

  32. Den Haan, J. M. M., Lehar, S. M. & Bevan, M. J. CD8+ but not CD8− dendritic cells cross-prime cytotoxic T cells in vivo. J. Exp. Med. 192, 1685–1695 (2000).First identification of a specialized cross-presenting APC.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Pooley, J. L., Heath, W. R. & Shortman, K. Cutting edge: intravenous soluble antigen is presented to CD4 T cells by CD8+ dendritic cells, but cross-presented to CD8 T cells by CD8+ dendritic cells. J. Immunol. 166, 5327–5330 (2001).

    CAS  PubMed  Google Scholar 

  34. Moser, M. & Murphy, K. M. Dendritic cell regulation of TH1–TH2 development. Nature Immunol. 1, 199–205 (2000).

    CAS  Google Scholar 

  35. Schulz, O. et al. CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity 13, 453–462 (2000).

    CAS  PubMed  Google Scholar 

  36. Hochrein, H. et al. Interleukin-4 is a major regulatory cytokine governing bioactive interleukin-12 production by mouse and human dendritic cells. J. Exp. Med. 192, 823–833 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Langenkamp, A., Messi, M., Lanzavecchia, A. & Sallusto, F. Kinetics of dendritic cell activation: impact on priming TH1, TH2, and nonpolarized T cells. Nature Immunol. 1, 311–316 (2001).

    Google Scholar 

  38. D'Ostiani, C. F. et al. Dendritic cells discriminate between yeasts and hyphae of the fungus Candida albicans. Implications for initiation of T helper cell immunity in vitro and in vivo. J. Exp. Med. 191, 1661–1674 (2000).Subtle discrimination by DCs and flexibility of function.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Iwasaki, A. & Kelsall, B. L. Localization of distinct Peyer's patch dendritic cell subsets and their recruitment by chemokines macrophage inflammatory protein (MIP)-3α, MIP-3β, and secondary lymphoid organ chemokine. J. Exp. Med. 191, 1381–1394 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Anjuère, F. et al. Definition of dendritic cell subpopulations present in the spleen, Peyer's patches, lymph nodes, and skin of the mouse. Blood 93, 590–598 (1999).

    PubMed  Google Scholar 

  41. Henri, S. et al. The dendritic cell populations of mouse lymph nodes. J. Immunol. 167, 741–748 (2001).

    CAS  PubMed  Google Scholar 

  42. Vremec, D., Pooley, J., Hochrein, H., Wu, L. & Shortman, K. CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen. J. Immunol. 164, 2978–2986 (2000).

    CAS  PubMed  Google Scholar 

  43. Reis e Sousa, C. et al. In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J. Exp. Med. 186, 1819–1829 (1997).

    CAS  PubMed  Google Scholar 

  44. De Smedt, T. et al. Regulation of dendritic cell numbers and maturation by lipopolysaccharides in vivo. J. Exp. Med. 184, 1413–1424 (1996).

    CAS  PubMed  Google Scholar 

  45. Inaba, K. et al. 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 (1993).Myeloid origin of DCs.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Izon, D. et al. A common pathway for dendritic cell and early B cell development. J. Immunol. 167, 1387–1392 (2001).

    CAS  PubMed  Google Scholar 

  47. Bjorck, P. & Kincade, P. W. CD19+ pro-B cells can give rise to dendritic cells in vitro. J. Immunol. 161, 5795–5799 (1998).

    CAS  PubMed  Google Scholar 

  48. Radtke, F. et al. Notch1 deficiency dissociates the intrathymic development of dendritic cells and T cells. J. Exp. Med. 191, 1085–1094 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Rodewald, H. R., Brocker, T. & Haller, C. Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice. Proc. Natl Acad. Sci. USA 96, 15068–15073 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Traver, D. et al. Development of CD8α+ dendritic cells from a common myeloid progenitor. Science 290, 2152–2154 (2000).

    CAS  PubMed  Google Scholar 

  51. Manz, M. G., Traver, D., Miyamoto, T., Weissman, I. L. & Akashi, K. Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood 97, 3333–3341 (2001).

    CAS  PubMed  Google Scholar 

  52. Wu, L., D'Amico, A., Hochrein, H., Shortman, K. & Lucas, K. Development of thymic and splenic dendritic cell populations from different hemopoietic precursors. Blood 98, 3376–3382 (2001).References 51 and 52 show that the DC subtype is not predetermined by the early haematopoietic precursor cell.

    CAS  PubMed  Google Scholar 

  53. Saunders, D. et al. Dendritic cell development in culture from thymic precursor cells in the absence of granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 184, 2185–2196 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. O'Keeffe, M. et al. Comparison of the effects of administration of Propenipoietin-1, Flt-3 ligand, G-CSF and PEGylated GM-CSF on dendritic cell subsets in the mouse. Blood (in press).

  55. Wu, L., Nichogiannopoulou, A., Shortman, K. & Georgopoulos, K. Cell-autonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage. Immunity 7, 483–492 (1997).

    CAS  PubMed  Google Scholar 

  56. Wu, L. et al. RelB is essential for the development of myeloid-related CD8α− dendritic cells but not of lymphoid-related CD8α+ dendritic cells. Immunity 9, 839–847 (1998).

    CAS  PubMed  Google Scholar 

  57. Guerriero, A., Langmuir, P. B., Spain, L. M. & Scott, E. W. PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells. Blood 95, 879–885 (2000).

    CAS  PubMed  Google Scholar 

  58. Kamath, A. et al. The development, maturation and turnover rate of mouse spleen dendritic cell populations. J. Immunol. 165, 6762–6770 (2000).

    CAS  PubMed  Google Scholar 

  59. Randolph, G. J., Inaba, K., Robbiani, D. F., Steinman, R. M. & Muller, W. A. Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. Immunity 11, 753–761 (1999).

    CAS  PubMed  Google Scholar 

  60. Asselin-Paturel, C. et al. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nature Immunol. 2, 1144–1150 (2001).The identification of the mouse equivalent of human plasmacytoid DC precursor.

    CAS  Google Scholar 

  61. Nakano, H., Yanagita, M. & Gunn, M. D. CD11c+B220+Gr-1+ cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells. J. Exp. Med. 194, 1171–1178 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Bjorck, P. Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte–macrophage colony-stimulating factor-treated mice. Blood 98, 3520–3526 (2001).

    CAS  PubMed  Google Scholar 

  63. Maldonado-López, R. et al. CD8α+ and CD8α− subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J. Exp. Med. 189, 587–592 (1999).

    PubMed  PubMed Central  Google Scholar 

  64. Pulendran, B. et al. Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Proc. Natl Acad. Sci. USA 96, 1036–1041 (1999).References 63 and 64 provide first evidence that different DC subtypes can determine the nature of T-cell responses.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Pulendran, B., Banchereau, J., Maraskovsky, E. & Maliszewski, C. Modulating the immune response with dendritic cells and their growth factors. Trends Immunol. 22, 41–47 (2001).

    CAS  PubMed  Google Scholar 

  66. Hochrein, H. et al. Differential production of IL-12, IFN-α, and IFN-γ by mouse dendritic cell subsets. J. Immunol. 166, 5448–5455 (2001).

    CAS  PubMed  Google Scholar 

  67. Kronin, V. et al. Differential effect of CD8+ and CD8− dendritic cells in the stimulation of secondary CD4+ T cells. Int. Immunol. 13, 465–473 (2001).

    CAS  PubMed  Google Scholar 

  68. Kronin, V. et al. A subclass of dendritic cells regulates the response of naive CD8 T cells by limiting their IL-2 production. J. Immunol. 157, 3819–3827 (1996).

    CAS  PubMed  Google Scholar 

  69. Winkel, K. D., Kronin, V., Krummel, M. F. & Shortman, K. The nature of the signals regulating CD8 T cell proliferative responses to CD8α+ or CD8α− dendritic cells. Eur. J. Immunol. 27, 3350–3359 (1997).

    CAS  PubMed  Google Scholar 

  70. Kronin, V., Hochrein, H., Shortman, K. & Kelso, A. The regulation of T cell cytokine production by dendritic cells. Immunol. Cell Biol. 78, 214–223 (2000).

    CAS  PubMed  Google Scholar 

  71. O'Connell, P. J. et al. CD8α+ (lymphoid-related) and CD8α− (myeloid) dendritic cells differentially regulate vascularized organ allograft survival. Transplant Proc. 33, 94 (2001).

    CAS  PubMed  Google Scholar 

  72. McIlroy, D. et al. Infection frequency of dendritic cells and CD4+ T lymphocytes in spleens of human immunodeficiency virus-positive patients. J. Virol. 69, 4737–4745 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Vandenabeele, S., Hochrein, H., Mavaddat, N., Winkel, K. & Shortman, K. Human thymus contains 2 distinct dendritic cell populations. Blood 97, 1733–1741 (2001).

    CAS  PubMed  Google Scholar 

  74. Bendriss-Vermare, N. et al. Human thymus contains IFN-α-producing CD11c−, myeloid CD11c+, and mature interdigitating dendritic cells. J. Clin. Invest. 107, 835–844 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Young, J. W., Szabolcs, P. & Moore, M. A. S. Identification of dendritic cell colony-forming units among normal human CD34+ bone marrow progenitors that are expanded by c-kit ligand and yield pure dendritic cell colonies in the presence of granulocyte/macrophage colony-stimulating factor and tumor necrosis factor α. J. Exp. Med. 182, 1111–1119 (1995).

    CAS  PubMed  Google Scholar 

  76. Caux, C. & Banchereau, J. in In vitro Regulation of Dendritic Cell Development and Function (eds A. Whetton & J. Gordon) 263–301 (Plenum Press: London, 1996).

    Google Scholar 

  77. Caux, C. et al. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM−CSF+TNFα. J. Exp. Med. 184, 695–706 (1996).Culture system showing two pathways of human DC development.

    CAS  PubMed  Google Scholar 

  78. Strunk, D., Egger, C., Leitner, G., Hanau, D. & Stingl, G. A skin homing molecule defines the Langerhans cell progenitor in human peripheral blood. J. Exp. Med. 185, 1131–1136 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Strobl, H. et al. TGF-β1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J. Immunol. 157, 1499–1507 (1996).

    CAS  PubMed  Google Scholar 

  80. Borkowski, T. A., Letterio, J. J., Farr, A. G. & Udey, M. C. A role for endogenous transforming growth factor β1 in Langerhans cell biology: the skin of transforming growth factor β1 null mice is devoid of epidermal Langerhans cells. J. Exp. Med. 184, 2417–2422 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Galy, A., Travis, M., Cen, D. & Chen, B. Human T, B, natural killer and dendritic cells arise from a common bone marrow progenitor cell subset. Immunity 3, 459–473 (1995).

    CAS  PubMed  Google Scholar 

  82. 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 α. J. Exp. Med. 179, 1109–1118 (1994).DCs from human blood monocytes in culture, the basis of much DC immunotherapy.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  84. Romani, N. et al. Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J. Immunol. Methods 196, 137–151 (1996).

    CAS  PubMed  Google Scholar 

  85. Randolph, G. J., Beaulieu, S., Lebecque, S., Steinman, R. M. & Muller, W. A. Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 282, 480–483 (1998).A culture model mimicking DC development in vivo.

    CAS  PubMed  Google Scholar 

  86. Rissoan, M. C. et al. Reciprocal control of T helper and dendritic cell differentiation. Science 283, 1183–1186 (1999).

    CAS  PubMed  Google Scholar 

  87. Grouard, G. et al. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J. Exp. Med. 185, 1101–1111 (1997).The original demonstration that plasmacytoid cells are DC precursors.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Res, P. C., Couwenberg, F., Vyth-Dreese, F. A. & Spits, H. Expression of pTα mRNA in a committed dendritic cell precursor in the human thymus. Blood 94, 2647–2657 (1999).

    CAS  PubMed  Google Scholar 

  89. Spits, H., Couwenberg, F., Bakker, A. Q., Weijer, K. & Uittenbogaart, C. H. Id2 and Id3 inhibit development of CD34+ stem cells into predendritic cell (pre-DC)2 but not into pre-DC1. Evidence for a lymphoid origin of pre-DC2. J. Exp. Med. 192, 1775–1784 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Tanaka, H., Demeure, C. E., Rubio, M., Delespesse, G. & Sarfati, M. Human monocyte-derived dendritic cells induce naive T cell differentiation into T helper cell type 2 (TH2) or TH1/TH2 effectors. Role of stimulator/responder ratio. J. Exp. Med. 192, 405–412 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Kalinski, P., Schuitemaker, J. H., Hilkens, C. M., Wierenga, E. A. & Kapsenberg, M. L. Final maturation of dendritic cells is associated with impaired responsiveness to IFN-γ and to bacterial IL-12 inducers: decreased ability of mature dendritic cells to produce IL-12 during the interaction with TH cells. J. Immunol. 162, 3231–3236 (1999).

    CAS  PubMed  Google Scholar 

  92. Huang, Q. et al. The plasticity of dendritic cell responses to pathogens and their components. Science 294, 870–875 (2001).

    CAS  PubMed  Google Scholar 

  93. Liu, Y. J. Dendritic cell subsets and lineages, and their functions in innate and adaptive immunity. Cell 106, 259–262 (2001).

    CAS  PubMed  Google Scholar 

  94. Liu, Y. J., Kanzler, H., Soumelis, V. & Gilliet, M. Dendritic cell lineage, plasticity and cross-regulation. Nature Immunol. 2, 585–589 (2001).

    CAS  Google Scholar 

  95. Alexopoulou, L., Holt, A. C., Medzhitov, R. & Flavell, R. A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732–738 (2001).

    CAS  PubMed  Google Scholar 

  96. Cella, M., Facchetti, F., Lanzavecchia, A. & Colonna, M. Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. Nature Immunol. 1, 305–310 (2000).

    CAS  Google Scholar 

Download references

Acknowledgements

We thank M. O'Keeffe, E. Maraskovsky and W. Heath for their suggestions, and A. Alafaci for preparing the manuscript.

Author information

Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Victoria, 3050, Australia

    Ken Shortman

  2. DNAX Research Institute, Palo Alto, 94304, California, USA

    Yong-Jun Liu

Authors
  1. Ken Shortman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong-Jun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASES

LocusLink

CD1a

CD4

CD8

CD8α

CD9

CD11b

CD11c

CD14

CD34

CD40

CD45

CD68

CD80

CD86

CD154

CD205

c-kit

coagulation factor XIIIa

γc−

E-cadherin

GM-CSF

GR-1

IFN-γ

IL-3

IL-4

IL-6

IL-18

langerin

L-selectin

Ly6C

Notch1

TLR1

TLR2

TLR3

TLR4

TLR5

TLR7

TLR8

TLR9

TNF-α

Glossary

DANGER

A term, popularized by P. Matzinger, that covers the various signals from damaged tissues or from microbial products that trigger dendritic cell activation.

ADJUVANT

A substance that enhances the immune response to antigens.

IMMATURE DCS

(iDCS.) These dendritic cells are typically found in non-lymphoid tissues and are capable of antigen uptake and processing, but as yet are unable to interact with T cells. They have intracellular but low or no surface MHC II, and do not yet express co-stimulator molecules.

ACTIVATED DCS

These dendritic cells are fully mature and express high surface levels of MHC II and co-stimulator molecules. They initiate T-cell immune responses.

QUIESCENT DCS

These dendritic cells are typically found in the lymphoid tissues of uninfected laboratory mice and are sufficiently mature to express moderate surface levels of MHC II and co-stimulator molecules, but they are not yet fully activated and maintain some potential for antigen uptake and processing. They might mediate T-cell tolerance.

CPG

Denotes a deoxynucleotide motif in bacterial DNA that acts as an adjuvant. It is recognized by, and activates, certain dendritic cells. The nucleotide sequence and methylation state of this portion of bacterial DNA differs from those of mammalian DNA.

TH1 AND TH2

T-helper cells have the potential to produce many cytokines. If suitably and extensively stimulated, two polarized patterns of cytokine production can emerge. TH1 cells characteristically produce high levels of interferon-γ and promote macrophage-mediated inflammatory responses. TH2 cells characteristically produce interleukins-4 and -5, and promote mast cell and eosinophil functions. In balanced immune responses, individual T cells show a range of cytokine production potentials, not just these extreme forms.

PRECURSOR DCS

(pDCs.) These dendritic cells are downstream of multipotent haematopoietic progenitors and are largely committed to dendritic cell production, but do not have the morphological appearance or functions of dendritic cells.

PLASMACYTOID

Having the morphological appearance of B-lineage antibody-producing plasma cells, including the presence of rough endoplasmic reticulum. Plasmacytoid dendritic cells do not, however, produce immunoglobulin and lack most B-lineage markers.

BIRBECK GRANULES

A characteristic structure that is visualized by electron microscopy in sections of Langerhans epidermal dendritic cells. They are believed to be a component of the antigen-processing system of these cells.

PRE-T-CELL RECEPTOR-α

The form of T-cell receptor-α that is expressed at early stages of T-cell development. It temporarily substitutes for the mature T-cell receptor-α-chain during a developmental checkpoint.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shortman, K., Liu, YJ. Mouse and human dendritic cell subtypes. Nat Rev Immunol 2, 151–161 (2002). https://doi.org/10.1038/nri746

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri746

This article is cited by

Search

Advanced 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