• 1
    Steinman, R. M., The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 1991. 9: 271296.
  • 2
    Reis e Sousa, C., Dendritic cells in a mature age. Nat. Rev. Immunol. 2006. 6: 476483.
  • 3
    Villadangos, J. A. and Schnorrer, P., Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat. Rev. Immunol. 2007. 7: 543555.
  • 4
    Shortman, K. and Naik, S. H., Steady-state and inflammatory dendritic-cell development. Nat. Rev. Immunol. 2007. 7: 1930.
  • 5
    Tacken, P. J., de Vries, I. J., Torensma, R. and Figdor, C. G., Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat. Rev. Immunol. 2007. 7: 790802.
  • 6
    Vallon-Eberhard, A., Landsman, L., Yogev, N., Verrier, B. and Jung, S., Transepithelial pathogen uptake into the small intestinal lamina propria. J. Immunol. 2006. 176: 24652469.
  • 7
    Laouar, Y., Sutterwala, F. S., Gorelik, L. and Flavell, R. A., Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma. Nat. Immunol. 2005. 6: 600607.
  • 8
    Huleatt, J. W. and Lefrancois, L., Antigen-driven induction of CD11c on intestinal intraepithelial lymphocytes and CD8+ T cells in vivo. J. Immunol. 1995. 154: 56845693.
  • 9
    Witmer-Pack, M. D., Swiggard, W. J., Mirza, A., Inaba, K. and Steinman, R. M., Tissue distribution of the DEC-205 protein that is detected by the monoclonal antibody NLDC-145. II. Expression in situ in lymphoid and nonlymphoid tissues. Cell Immunol. 1995. 163: 157162.
  • 10
    Inaba, K., Swiggard, W. J., Inaba, M., Meltzer, J., Mirza, A., Sasagawa, T., Nussenzweig, M. C. and Steinman, R. M., Tissue distribution of the DEC-205 protein that is detected by the monoclonal antibody NLDC-145. I. Expression on dendritic cells and other subsets of mouse leukocytes. Cell Immunol. 1995. 163: 148156.
  • 11
    Castro, F. V., Tutt, A. L., White, A. L., Teeling, J. L., James, S., French, R. R. and Glennie, M. J., CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses. Eur. J. Immunol. 2008. 38: 22632273.
  • 12
    Wang, H., Griffiths, M. N., Burton, D. R. and Ghazal, P., Rapid antibody responses by low-dose, single-step, dendritic cell-targeted immunization. Proc. Natl. Acad. Sci. USA 2000. 97: 847852.
  • 13
    Bonifaz, L. C., Bonnyay, D. P., Charalambous, A., Darguste, D. I., Fujii, S., Soares, H., Brimnes, M. K. et al., In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J. Exp. Med. 2004. 199: 815824.
  • 14
    Hawiger, D., Inaba, K., Dorsett, Y., Guo, M., Mahnke, K., Rivera, M., Ravetch, J. V. et al., Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 2001. 194: 769779.
  • 15
    Tagliani, E., Guermonprez, P., Sepulveda, J., Lopez-Bravo, M., Ardavin, C., Amigorena, S., Benvenuti, F. and Burrone, O. R., Selection of an antibody library identifies a pathway to induce immunity by targeting CD36 on steady-state CD8alpha+ dendritic cells. J. Immunol. 2008. 180: 32013209.
  • 16
    He, L. Z., Crocker, A., Lee, J., Mendoza-Ramirez, J., Wang, X. T., Vitale, L. A. and O'Neill, T., Antigenic targeting of the human mannose receptor induces tumor immunity. J. Immunol. 2007. 178: 62596267.
  • 17
    Delneste, Y., Magistrelli, G., Gauchat, J., Haeuw, J., Aubry, J., Nakamura, K., Kawakami-Honda, N. et al., Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity 2002. 17: 353362.
  • 18
    Bourges, D., Zhan, Y., Brady, J. L., Braley, H., Caminschi, I., Prato, S., Villadangos, J. A. and Lew, A. M., Targeting the gut vascular endothelium induces gut effector CD8 T cell responses via cross-presentation by dendritic cells. J. Immunol. 2007. 179: 56785685.
  • 19
    Caminschi, I., Proietto, A. I., Ahmet, F., Kitsoulis, S., Shin Teh, J., Lo, J. C., Rizzitelli, A. et al., The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement. Blood 2008. 112: 32643273.
  • 20
    Bennett, S. R., Carbone, F. R., Toy, T., Miller, J. F. and Heath, W. R., B cells directly tolerize CD8(+) T cells. J. Exp. Med. 1998. 188: 19771983.
  • 21
    Delamarre, L., Pack, M., Chang, H., Mellman, I. and Trombetta, E. S., Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science 2005. 307: 16301634.
  • 22
    Burgdorf, S., Kautz, A., Bohnert, V., Knolle, P. A. and Kurts, C., Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation. Science 2007. 316: 612616.
  • 23
    Idoyaga, J., Cheong, C., Suda, K., Suda, N., Kim, J. Y., Lee, H., Park, C. G. and Steinman, R. M., Cutting edge: Langerin/CD207 receptor on dendritic cells mediates efficient antigen presentation on MHC I and II products in vivo. J. Immunol. 2008. 180: 36473650.
  • 24
    Dudziak, D., Kamphorst, A. O., Heidkamp, G. F., Buchholz, V. R., Trumpfheller, C., Yamazaki, S. and Cheong, C., Differential antigen processing by dendritic cell subsets in vivo. Science 2007. 315: 107111.
  • 25
    Carter, R. W., Thompson, C., Reid, D. M., Wong, S. Y. and Tough, D. F., Preferential induction of CD4+ T cell responses through in vivo targeting of antigen to dendritic cell-associated C-type lectin-1. J. Immunol. 2006. 177: 22762284.
  • 26
    Caminschi, I., Vandenabeele, S., Sofi, M., McKnight, A. J., Ward, N., Brodnicki, T. C. and Toy, T., Gene structure and transcript analysis of the human and mouse EGF-TM7 molecule, FIRE. DNA Seq. 2006. 17: 814.
  • 27
    Hamann, J., Kwakkenbos, M. J., de Jong, E. C., Heus, H., Olsen, A. S. and van Lier, R. A., Inactivation of the EGF-TM7 receptor EMR4 after the Pan-Homo divergence. Eur. J. Immunol. 2003. 33: 13651371.
  • 28
    Sancho, D., Mourao-Sa, D., Joffre, O. P., Schulz, O., Rogers, N. C., Pennington, D. J., Carlyle, J. R. and Reis e Sousa, C., Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin. J. Clin. Invest. 2008. 118: 20982110.
  • 29
    Galibert, L., Diemer, G. S., Liu, Z., Johnson, R. S., Smith, J. L., Walzer, T., Comeau, M. R. et al., Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated molecule. J. Biol. Chem. 2005. 280: 2195521964.
  • 30
    den Haan, J. M., Lehar, S. M. and Bevan, M. J., CD8(+) but not CD8(−) dendritic cells cross-prime cytotoxic T cells in vivo. J. Exp. Med. 2000. 192: 16851696.
  • 31
    Pooley, J., Heath, W. R. and Shortman, K., 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. 2001. 166: 53275330.
  • 32
    Schnorrer, P., Behrens, G. M., Wilson, N. S., Pooley, J. L., Smith, C. M., El-Sukkari, D. and Davey, G., The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture. Proc. Natl. Acad. Sci. USA 2006. 103: 1072910734.
  • 33
    Hochrein, H., Shortman, K., Vremec, D., Scott, B., Hertzog, P., and O'Keeffe, M., Differential production of IL-12, IFN-alpha, and IFN-gamma by mouse dendritic cell subsets. J. Immunol. 2001. 166: 54485455.
  • 34
    Reis e Sousa, C., Hieny, S., Scharton-Kersten, T., Jankovic, D., Charest, H., Germain, R. N. and Sher, A., 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. 1997. 186: 18191829.
  • 35
    Maldonado-Lopez, R., De Smedt, T., Michel, P., Godfroid, J., Pajak, B., Heirman, C., Thielemans, K. et al., CD8alpha+ and CD8alpha- subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J. Exp. Med. 1999. 189: 587592.
  • 36
    Pulendran, B., Smith, J. L., Caspary, G., Brasel, K., Pettit, D., Maraskovsky, E. and Maliszewski, C. R., Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Proc. Natl. Acad. Sci. USA 1999. 96: 10361041.
  • 37
    Corbett, A. J., Caminschi, I., McKenzie, B. S., Brady, J. L., Wright, M. D., Mottram, P. L., Hogarth, P. M. et al., Antigen delivery via two molecules on the CD8- dendritic cell subset induces humoral immunity in the absence of conventional “danger”. Eur. J. Immunol. 2005. 35: 28152825.
  • 38
    Soares, H., Waechter, H., Glaichenhaus, N., Mougneau, E., Yagita, H., Mizenina, O. and Dudziak, D., A subset of dendritic cells induces CD4+ T cells to produce IFN-gamma by an IL-12-independent but CD70-dependent mechanism in vivo. J. Exp. Med. 2007. 204: 10951106.
  • 39
    Finkelman, F. D., Lees, A., Birnbaum, R., Gause, W. C. and Morris, S. C., Dendritic cells can present antigen in vivo in a tolerogenic or immunogenic fashion. J. Immunol. 1996. 157: 14061414.
  • 40
    Bonifaz, L., Bonnyay, D., Mahnke, K., Rivera, M., Nussenzweig, M. C. and Steinman, R. M., 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. 2002. 196: 16271638.
  • 41
    Boscardin, S. B., Hafalla, J. C., Masilamani, R. F., Kamphorst, A. O., Zebroski, H. A., Rai, U., Morrot, A. et al., Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses. J. Exp. Med. 2006. 203: 599606.
  • 42
    Charalambous, A., Oks, M., Nchinda, G., Yamazaki, S. and Steinman, R. M., Dendritic cell targeting of survivin protein in a xenogeneic form elicits strong CD4+ T cell immunity to mouse survivin. J. Immunol. 2006. 177: 84108421.
  • 43
    Do, Y., Park, C. G., Kang, Y. S., Park, S. H., Lynch, R. M., Lee, H., Powell, B. S. and Steinman, R. M., Broad T cell immunity to the LcrV virulence protein is induced by targeted delivery to DEC-205/CD205-positive mouse dendritic cells. Eur. J. Immunol. 2008. 38: 2029.
  • 44
    Trumpfheller, C., Caskey, M., Nchinda, G., Longhi, M. P., Mizenina, O., Huang, Y., Schlesinger, S. J. et al., The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc. Natl. Acad. Sci. USA 2008. 105: 25742579.
  • 45
    Trumpfheller, C., Finke, J. S., Lopez, C. B., Moran, T. M., Moltedo, B., Soares, H., Huang, Y. et al., Intensified and protective CD4+ T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine. J. Exp. Med. 2006. 203: 607617.
  • 46
    Mahnke, K., Qian, Y., Fondel, S., Brueck, J., Becker, C. and Enk, A. H., Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice. Cancer Res. 2005. 65: 70077012.
  • 47
    van Broekhoven, C. L., Parish, C. R., Demangel, C., Britton, W. J. and Altin, J. G., Targeting dendritic cells with antigen-containing liposomes: a highly effective procedure for induction of antitumor immunity and for tumor immunotherapy. Cancer Res. 2004. 64: 43574365.
  • 48
    Mahnke, K., Qian, Y., Knop, J. and Enk, A. H., Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood 2003. 101: 48624869.
  • 49
    Kretschmer, K., Apostolou, I., Hawiger, D., Khazaie, K., Nussenzweig, M. C. and von Boehmer, H., Inducing and expanding regulatory T cell populations by foreign antigen. Nat. Immunol. 2005. 6: 12191227.
  • 50
    Yamazaki, S., Dudziak, D., Heidkamp, G. F., Fiorese, C., Bonito, A. J., Inaba, K., Nussenzweig, M. C. and Steinman, R. M., CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells. J. Immunol. 2008. 181: 69236933.
  • 51
    Bruder, D., Westendorf, A. M., Hansen, W., Prettin, S., Gruber, A. D., Qian, Y., von Boehmer, H. et al., On the edge of autoimmunity: T-cell stimulation by steady-state dendritic cells prevents autoimmune diabetes. Diabetes 2005. 54: 33953401.
  • 52
    Mukhopadhaya, A., Hanafusa, T., Jarchum, I., Chen, Y. G., Iwai, Y., Serreze, D. V., Steinman, R. M. et al., Selective delivery of {beta} cell antigen to dendritic cells in vivo leads to deletion and tolerance of autoreactive CD8+ T cells in NOD mice. Proc. Natl. Acad. Sci. USA 2008. 105: 63746379.
  • 53
    Carayanniotis, G. and Barber, B. H., Adjuvant-free IgG responses induced with antigen coupled to antibodies against class II MHC. Nature 1987. 327: 5961.
  • 54
    Snider, D. P., Kaubisch, A. and Segal, D. M., Enhanced antigen immunogenicity induced by bispecific antibodies. J. Exp. Med. 1990. 171: 19571963.
  • 55
    Skea, D. L. and Barber, B. H., Studies of the adjuvant-independent antibody response to immunotargeting. Target structure dependence, isotype distribution, and induction of long term memory. J. Immunol. 1993. 151: 35573568.
  • 56
    Barr, T. A., McCormick, A. L., Carlring, J. and Heath, A. W., A potent adjuvant effect of CD40 antibody attached to antigen. Immunology 2003. 109: 8792.
  • 57
    Huysamen, C., Willment, J. A., Dennehy, K. M. and Brown, G. D., CLEC9A is a novel activation C-type lectin-like receptor expressed on BDCA3+ dendritic cells and a subset of monocytes. J. Biol. Chem. 2008 283: 1669316701.
  • 58
    Bozzacco, L., Trumpfheller, C., Siegal, F. P., Mehandru, S., Markowitz, M., Carrington, M., Nussenzweig, M. C. 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 2007. 104: 12891294.
  • 59
    Bennett, S. R., Carbone, F. R., Karamalis, F., Miller, J. F. and Heath, W. R., Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help. J. Exp. Med. 1997. 186: 6570.
  • 60
    Janssen, E. M., Lemmens, E. E., Wolfe, T., Christen, U., Von Herrath, M. G. and Schoenberger, S. P., CD4(+) T cells are required for secondary expansion and memory in CD8(+) T lymphocytes. Nature 2003. 421: 852856.
  • 61
    Smith, C. M., Wilson, N. S., Waithman, J., Villadangos, J. A., Carbone, F. R., Heath, W. R. and Belz, G. T., Cognate CD4(+) T cell licensing of dendritic cells in CD8(+) T cell immunity. Nat. Immunol. 2004. 5: 11431148.
  • 62
    Curtsinger, J. M., Lins, D. C. and Mescher, M. F., Signal 3 determines tolerance versus full activation of naive CD8 T cells: dissociating proliferation and development of effector function. J. Exp. Med. 2003. 197: 11411151.
  • 63
    Iyoda, T., Shimoyama, S., Liu, K., Omatsu, Y., Akiyama, Y., Maeda, Y., Takahara, K. et al.,The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo. J. Exp. Med. 2002. 195: 12891302.
  • 64
    Nurieva, R. I., Chung, Y., Hwang, D., Yang, X. O., Kang, H. S., Ma, L. and Wang, Y. H., Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 2008. 29: 138149.
  • 65
    Vogelzang, A., McGuire, H. M., Yu, D., Sprent, J., Mackay, C. R. and King, C., A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity 2008. 29: 127137.
  • 66
    Eddahri, F., Denanglaire, S., Bureau, F., Spolski, R., Leonard, W. J., Leo, O. and Andris, F., Interleukin-6 / STAT3 signalling regulates the ability of naive T cells to acquire B cell help capacities. Blood 2008. DOI: 10.1182/blood-2008-04-154682.
  • 67
    Wykes, M., Pombo, A., Jenkins, C. and MacPherson, G. G., Dendritic cells interact directly with naive B lymphocytes to transfer antigen and initiate class switching in a primary T-dependent response. J. Immunol. 1998. 161: 13131319.
  • 68
    Pereira, C. F., Torensma, R., Hebeda, K., Kretz-Rommel, A., Faas, S. J., Figdor, C. G. and Adema, G. J., In vivo targeting of DC-SIGN-positive antigen-presenting cells in a nonhuman primate model. J. Immunother. 2007. 30: 705714.
  • 69
    Tacken, P. J., de Vries, I. J., Gijzen, K., Joosten, B., Wu, D., Rother, R. P., Faas, S. J. et al., Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti-DC-SIGN antibody. Blood 2005. 106: 12781285.
  • 70
    Gurer, C., Strowig, T., Brilot, F., Pack, M., Trumpfheller, C., Arrey, F., Park, C. G. et al., Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses. Blood 2008. 112: 12311239.
  • 71
    Meyer-Wentrup, F., Benitez-Ribas, D., Tacken, P. J., Punt, C. J., Figdor, C. G., de Vries, I. J. and Adema, G. J., Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-alpha production. Blood 2008. 111: 42454253.
  • 72
    Ramakrishna, V., Treml, J. F., Vitale, L., Connolly, J. E., O'Neill, T., Smith, P. A., Jones, C. L. et al., Mannose receptor targeting of tumor antigen pmel17 to human dendritic cells directs anti-melanoma T cell responses via multiple HLA molecules. J. Immunol. 2004. 172: 28452852.
  • 73
    He, L. Z., Ramakrishna, V., Connolly, J. E., Wang, X. T., Smith, P. A., Jones, C. L. and Valkova-Valchanova, M., A novel human cancer vaccine elicits cellular responses to the tumor-associated antigen, human chorionic gonadotropin beta. Clin Cancer Res. 2004. 10: 19201927.
  • 74
    Kretz-Rommel, A., Qin, F., Dakappagari, N., Torensma, R., Faas, S., Wu, D. and Bowdish, K. S., In vivo targeting of antigens to human dendritic cells through DC-SIGN elicits stimulatory immune responses and inhibits tumor growth in grafted mouse models. J. Immunother. 2007. 30: 715726.