J. Exp. Med., Volume 189, Number 3, February 1, 1999 593-598

Antigen-pulsed CD8⁺ Dendritic Cells Generate an Immune Response after Subcutaneous Injection without Homing to the Draining Lymph Node

By Adrian L. Smith and Barbara Fazekas de St. Groth

From the Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia, 2042

Two subsets of murine splenic dendritic cells, derived from distinct precursors, can be distinguished by surface expression of CD8 homodimers. The functions of the two subsets remain controversial, although it has been suggested that the lymphoid-derived (CD8⁺) subset induces tolerance, whereas the myeloid-derived (CD8) subset has been shown to prime naive T cells and to generate memory responses. To study their capacity to prime or tolerize naive CD4⁺ T cells in vivo, purified CD8⁺ or CD8 dendritic cells were injected subcutaneously into normal mice. In contrast to CD8 dendritic cells, the CD8⁺ fraction failed to traffic to the draining lymph node and did not generate responses to intravenous peptide. However, after in vitro pulsing with peptide, strong in vivo T cell responses to purified CD8⁺ dendritic cells could be detected. Such responses may have been initiated via transfer of peptide-major histocompatibility complex complexes to migratory host CD8 dendritic cells after injection. These data suggest that correlation of T helper cell type 1 (Th1) and Th2 priming with injection of CD8⁺ and CD8 dendritic cells, respectively, may not result from direct T cell activation by lymphoid versus myeloid dendritic cells, but rather from indirect modification of the response to immunogenic CD8 dendritic cells by CD8⁺ dendritic cells.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Shklovskaya, E., Roediger, B., Fazekas de St. Groth, B. (2008). Epidermal and Dermal Dendritic Cells Display Differential Activation and Migratory Behavior While Sharing the Ability to Stimulate CD4+ T Cell Proliferation In Vivo. J. Immunol. 181: 418-430 [Abstract] [Full Text]  
• Pascale, F., Contreras, V., Bonneau, M., Courbet, A., Chilmonczyk, S., Bevilacqua, C., Eparaud, M., Niborski, V., Riffault, S., Balazuc, A.-M., Foulon, E., Guzylack-Piriou, L., Riteau, B., Hope, J., Bertho, N., Charley, B., Schwartz-Cornil, I. (2008). Plasmacytoid Dendritic Cells Migrate in Afferent Skin Lymph. J. Immunol. 180: 5963-5972 [Abstract] [Full Text]  
• Segura, E., Guerin, C., Hogg, N., Amigorena, S., Thery, C. (2007). CD8+ Dendritic Cells Use LFA-1 to Capture MHC-Peptide Complexes from Exosomes In Vivo. J. Immunol. 179: 1489-1496 [Abstract] [Full Text]  
• Liu, S., Foster, B. A., Chen, T., Zheng, G., Chen, A. (2007). Modifying Dendritic Cells via Protein Transfer for Antitumor Therapeutics. Clin. Cancer Res. 13: 283-291 [Abstract] [Full Text]  
• Berhanu, A., Huang, J., Alber, S. M., Watkins, S. C., Storkus, W. J. (2006). Combinational FLt3 Ligand and Granulocyte Macrophage Colony-Stimulating Factor Treatment Promotes Enhanced Tumor Infiltration by Dendritic Cells and Antitumor CD8+ T-Cell Cross-priming but Is Ineffective as a Therapy.. Cancer Res. 66: 4895-4903 [Abstract] [Full Text]  
• Seddiki, N., Santner-Nanan, B., Tangye, S. G., Alexander, S. I., Solomon, M., Lee, S., Nanan, R., de Saint Groth, B. F. (2006). Persistence of naive CD45RA+ regulatory T cells in adult life. Blood 107: 2830-2838 [Abstract] [Full Text]  
• Segura, E., Nicco, C., Lombard, B., Veron, P., Raposo, G., Batteux, F., Amigorena, S., Thery, C. (2005). ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood 106: 216-223 [Abstract] [Full Text]  
• Andre, F., Chaput, N., Schartz, N. E. C., Flament, C., Aubert, N., Bernard, J., Lemonnier, F., Raposo, G., Escudier, B., Hsu, D.-H., Tursz, T., Amigorena, S., Angevin, E., Zitvogel, L. (2004). Exosomes as Potent Cell-Free Peptide-Based Vaccine. I. Dendritic Cell-Derived Exosomes Transfer Functional MHC Class I/Peptide Complexes to Dendritic Cells. J. Immunol. 172: 2126-2136 [Abstract] [Full Text]  
• Colvin, B. L., Morelli, A. E., Logar, A. J., Lau, A. H., Thomson, A. W. (2004). Comparative evaluation of CC chemokine-induced migration of murine CD8{alpha}+ and CD8{alpha}- dendritic cells and their in vivo trafficking. J. Leukoc. Biol. 75: 275-285 [Abstract] [Full Text]  
• Matsuyoshi, H., Senju, S., Hirata, S., Yoshitake, Y., Uemura, Y., Nishimura, Y. (2004). Enhanced Priming of Antigen-Specific CTLs In Vivo by Embryonic Stem Cell-Derived Dendritic Cells Expressing Chemokine Along with Antigenic Protein: Application to Antitumor Vaccination. J. Immunol. 172: 776-786 [Abstract] [Full Text]  
• Sporri, R., Reis e Sousa, C. (2003). Newly Activated T Cells Promote Maturation of Bystander Dendritic Cells but Not IL-12 Production. J. Immunol. 171: 6406-6413 [Abstract] [Full Text]  
• van den Broeke, L. T., Daschbach, E., Thomas, E. K., Andringa, G., Berzofsky, J. A. (2003). Dendritic Cell-Induced Activation of Adaptive and Innate Antitumor Immunity. J. Immunol. 171: 5842-5852 [Abstract] [Full Text]  
• Shah, J. A., Darrah, P. A., Ambrozak, D. R., Turon, T. N., Mendez, S., Kirman, J., Wu, C.-Y., Glaichenhaus, N., Seder, R. A. (2003). Dendritic Cells Are Responsible for the Capacity of CpG Oligodeoxynucleotides to Act as an Adjuvant for Protective Vaccine Immunity Against Leishmania major in Mice. J. Exp. Med. 198: 281-291 [Abstract] [Full Text]  
• Hou, W., Wu, Y., Sun, S., Shi, M., Sun, Y., Yang, C., Pei, G., Gu, Y., Zhong, C., Sun, B. (2003). Pertussis Toxin Enhances Th1 Responses by Stimulation of Dendritic Cells. J. Immunol. 170: 1728-1736 [Abstract] [Full Text]  
• den Haan, J. M.M., Bevan, M. J. (2002). Constitutive versus Activation-dependent Cross-Presentation of Immune Complexes by CD8+ and CD8- Dendritic Cells In Vivo. J. Exp. Med. 196: 817-827 [Abstract] [Full Text]  
• Olasz, E. B., Linton, J., Katz, S. I. (2002). Soluble proteins and haptens on bone marrow-derived dendritic cells are presented to host CD4 T cells in an MHC-restricted manner. Int Immunol 14: 493-502 [Abstract] [Full Text]  
• McLellan, A. D., Kapp, M., Eggert, A., Linden, C., Bommhardt, U., Brocker, E.-B., Kammerer, U., Kampgen, E. (2002). Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression. Blood 99: 2084-2093 [Abstract] [Full Text]  
• MacDonald, A. S., Straw, A. D., Dalton, N. M., Pearce, E. J. (2002). Cutting Edge: Th2 Response Induction by Dendritic Cells: A Role for CD40. J. Immunol. 168: 537-540 [Abstract] [Full Text]  
• O'Connell, P. J., Li, W., Wang, Z., Specht, S. M., Logar, A. J., Thomson, A. W. (2002). Immature and Mature CD8{alpha}+ Dendritic Cells Prolong the Survival of Vascularized Heart Allografts. J. Immunol. 168: 143-154 [Abstract] [Full Text]  
• Schlecht, G., Leclerc, C., Dadaglio, G. (2001). Induction of CTL and Nonpolarized Th Cell Responses by CD8{alpha}+ and CD8{alpha}- Dendritic Cells. J. Immunol. 167: 4215-4221 [Abstract] [Full Text]  
• Caminschi, I., Lucas, K. M., O'Keeffe, M. A., Hochrein, H., Laabi, Y., Kontgen, F., Lew, A. M., Shortman, K., Wright, M. D. (2001). Molecular Cloning of F4/80-Like-Receptor, a Seven-Span Membrane Protein Expressed Differentially by Dendritic Cell and Monocyte-Macrophage Subpopulations. J. Immunol. 167: 3570-3576 [Abstract] [Full Text]  
• Fields, M. L., Sokol, C. L., Eaton-Bassiri, A., Seo, S.-j., Madaio, M. P., Erikson, J. (2001). Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells. J. Immunol. 167: 2370-2378 [Abstract] [Full Text]  
• Bertolino, P., Bowen, D. G., McCaughan, G. W., Fazekas de St. Groth, B. (2001). Antigen-Specific Primary Activation of CD8+ T Cells Within the Liver. J. Immunol. 166: 5430-5438 [Abstract] [Full Text]  
• Fukao, T., Frucht, D. M., Yap, G., Gadina, M., O'Shea, J. J., Koyasu, S. (2001). Inducible Expression of Stat4 in Dendritic Cells and Macrophages and Its Critical Role in Innate and Adaptive Immune Responses. J. Immunol. 166: 4446-4455 [Abstract] [Full Text]  
• Harshyne, L. A., Watkins, S. C., Gambotto, A., Barratt-Boyes, S. M. (2001). Dendritic Cells Acquire Antigens from Live Cells for Cross-Presentation to CTL. J. Immunol. 166: 3717-3723 [Abstract] [Full Text]  
• Delemarre, F. G. A., Hoogeveen, P. G., de Haan-Meulman, M., Simons, P. J., Drexhage, H. A. (2001). Homotypic cluster formation of dendritic cells, a close correlate of their state of maturation. Defects in the biobreeding diabetes-prone rat. J. Leukoc. Biol. 69: 373-380 [Abstract] [Full Text]  
• Drake, D. R. III, Shawver, M. L., Hadley, A., Butz, E., Maliszewski, C., Lukacher, A. E. (2001). Induction of Polyomavirus-Specific CD8+ T Lymphocytes by Distinct Dendritic Cell Subpopulations. J. Virol. 75: 544-547 [Abstract] [Full Text]  
• Grohmann, U., Fallarino, F., Silla, S., Bianchi, R., Belladonna, M. L., Vacca, C., Micheletti, A., Fioretti, M. C., Puccetti, P. (2001). CD40 Ligation Ablates the Tolerogenic Potential of Lymphoid Dendritic Cells. J. Immunol. 166: 277-283 [Abstract] [Full Text]  
• den Haan, J. M.M., Lehar, S. M., Bevan, M. J. (2000). CD8+ but Not CD8- Dendritic Cells Cross-prime Cytotoxic T Cells In Vivo. J. Exp. Med. 192: 1685-1696 [Abstract] [Full Text]  
• Yang, Y.-F., Tomura, M., Ono, S., Hamaoka, T., Fujiwara, H. (2000). Requirement for IFN-{gamma} in IL-12 production induced by collaboration between V{alpha}14+ NKT cells and antigen-presenting cells. Int Immunol 12: 1669-1675 [Abstract] [Full Text]  
• den Haan, J. M. M., Bevan, M. J. (2000). A novel helper role for CD4 T cells. Proc. Natl. Acad. Sci. USA 97: 12950-12952 [Full Text]  
• Martin, P., del Hoyo, G. M., Anjuere, F., Ruiz, S. R., Arias, C. F., Marin, A. R., Ardavin, C. (2000). Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8alpha - and CD8alpha + dendritic cells are generated from CD4low lymphoid-committed precursors. Blood 96: 2511-2519 [Abstract] [Full Text]  
• Grohmann, U., Bianchi, R., Belladonna, M. L., Silla, S., Fallarino, F., Fioretti, M. C., Puccetti, P. (2000). IFN-{gamma} Inhibits Presentation of a Tumor/Self Peptide by CD8{alpha}- Dendritic Cells Via Potentiation of the CD8{alpha}+ Subset. J. Immunol. 165: 1357-1363 [Abstract] [Full Text]  
• O'Connell, P. J., Morelli, A. E., Logar, A. J., Thomson, A. W. (2000). Phenotypic and Functional Characterization of Mouse Hepatic CD8{alpha}+ Lymphoid-Related Dendritic Cells. J. Immunol. 165: 795-803 [Abstract] [Full Text]  
• Glimcher, L. H., Murphy, K. M. (2000). Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev. 14: 1693-1711 [Full Text]  
• Mach, N., Gillessen, S., Wilson, S. B., Sheehan, C., Mihm, M., Dranoff, G. (2000). Differences in Dendritic Cells Stimulated in Vivo by Tumors Engineered to Secrete Granulocyte-Macrophage Colony-stimulating Factor or Flt3-Ligand. Cancer Res. 60: 3239-3246 [Abstract] [Full Text]  
• d'Ostiani, C. F., Del Sero, G., Bacci, A., Montagnoli, C., Spreca, A., Mencacci, A., Ricciardi-Castagnoli, P., Romani, L. (2000). 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 [Abstract] [Full Text]  
• Liu, Y.-J., Blom, B. (2000). Introduction: TH2-inducing DC2 for immunotherapy. Blood 95: 2482-2483 [Full Text]  
• Lambrecht, B. N., Pauwels, R. A., Fazekas de St. Groth, B. (2000). Induction of Rapid T Cell Activation, Division, and Recirculation by Intratracheal Injection of Dendritic Cells in a TCR Transgenic Model. J. Immunol. 164: 2937-2946 [Abstract] [Full Text]  
• Barratt-Boyes, S. M., Zimmer, M. I., Harshyne, L. A., Meyer, E. M., Watkins, S. C., Capuano, S. III, Murphey-Corb, M., Falo, L. D. Jr., Donnenberg, A. D. (2000). Maturation and Trafficking of Monocyte-Derived Dendritic Cells in Monkeys: Implications for Dendritic Cell-Based Vaccines. J. Immunol. 164: 2487-2495 [Abstract] [Full Text]  
• Fukao, T., Matsuda, S., Koyasu, S. (2000). Synergistic Effects of IL-4 and IL-18 on IL-12-Dependent IFN-{gamma} Production by Dendritic Cells. J. Immunol. 164: 64-71 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS