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^a Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave. #176, New York, NY 10021.212-327-8875212-327-8110

dhodapm{at}rockvax.rockefeller.edu

Immunostimulatory properties of dendritic cells (DCs) are linked to their maturation state. Injection of mature DCs rapidly enhances antigen-specific CD4⁺ and CD8⁺ T cell immunity in humans. Here we describe the immune response to a single injection of immature DCs pulsed with influenza matrix peptide (MP) and keyhole limpet hemocyanin (KLH) in two healthy subjects. In contrast to prior findings using mature DCs, injection of immature DCs in both subjects led to the specific inhibition of MP-specific CD8⁺ T cell effector function in freshly isolated T cells and the appearance of MP-specific interleukin 10–producing cells. When pre- and postimmunization T cells were boosted in culture, there were greater numbers of MP-specific major histocompatibility complex tetramer-binding cells after immunization, but these had reduced interferon production and lacked killer activity. These data demonstrate the feasibility of antigen-specific inhibition of effector T cell function in vivo in humans and urge caution with the use of immature DCs when trying to enhance tumor or microbial immunity.

Key Words: dendritic cells • maturation • tolerance • CD8⁺ T cells • immunization

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• Demaria, S., Santori, F. R., Ng, B., Liebes, L., Formenti, S. C., Vukmanovic, S. (2005). Select forms of tumor cell apoptosis induce dendritic cell maturation. J. Leukoc. Biol. 77: 361-368 [Abstract] [Full Text]  
• Radeke, H. H., von Wenckstern, H., Stoidtner, K., Sauer, B., Hammer, S., Kleuser, B. (2005). Overlapping Signaling Pathways of Sphingosine 1-Phosphate and TGF-{beta} in the Murine Langerhans Cell Line XS52. J. Immunol. 174: 2778-2786 [Abstract] [Full Text]  
• MacDonald, K. P. A., Rowe, V., Clouston, A. D., Welply, J. K., Kuns, R. D., Ferrara, J. L. M., Thomas, R., Hill, G. R. (2005). Cytokine Expanded Myeloid Precursors Function as Regulatory Antigen-Presenting Cells and Promote Tolerance through IL-10-Producing Regulatory T Cells. J. Immunol. 174: 1841-1850 [Abstract] [Full Text]  
• Hirata, S., Senju, S., Matsuyoshi, H., Fukuma, D., Uemura, Y., Nishimura, Y. (2005). Prevention of Experimental Autoimmune Encephalomyelitis by Transfer of Embryonic Stem Cell-Derived Dendritic Cells Expressing Myelin Oligodendrocyte Glycoprotein Peptide along with TRAIL or Programmed Death-1 Ligand. J. Immunol. 174: 1888-1897 [Abstract] [Full Text]  
• Levings, M. K., Gregori, S., Tresoldi, E., Cazzaniga, S., Bonini, C., Roncarolo, M. G. (2005). Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood 105: 1162-1169 [Abstract] [Full Text]  
• Herring, A. C., Falkowski, N. R., Chen, G.-H., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2005). Transient Neutralization of Tumor Necrosis Factor Alpha Can Produce a Chronic Fungal Infection in an Immunocompetent Host: Potential Role of Immature Dendritic Cells. Infect. Immun. 73: 39-49 [Abstract] [Full Text]  
• Bonnotte, B., Crittenden, M., Larmonier, N., Gough, M., Vile, R. G. (2004). MIP-3{alpha} Transfection into a Rodent Tumor Cell Line Increases Intratumoral Dendritic Cell Infiltration but Enhances (Facilitates) Tumor Growth and Decreases Immunogenicity. J. Immunol. 173: 4929-4935 [Abstract] [Full Text]  
• O'Neill, D. W., Adams, S., Bhardwaj, N. (2004). Manipulating dendritic cell biology for the active immunotherapy of cancer. Blood 104: 2235-2246 [Abstract] [Full Text]  
• Haase, C., Skak, K., Michelsen, B. K., Markholst, H. (2004). Local Activation of Dendritic Cells Leads to Insulitis and Development of Insulin-Dependent Diabetes in Transgenic Mice Expressing CD154 on the Pancreatic {beta}-Cells. Diabetes 53: 2588-2595 [Abstract] [Full Text]  
• Moseman, E. A., Liang, X., Dawson, A. J., Panoskaltsis-Mortari, A., Krieg, A. M., Liu, Y.-J., Blazar, B. R., Chen, W. (2004). Human Plasmacytoid Dendritic Cells Activated by CpG Oligodeoxynucleotides Induce the Generation of CD4+CD25+ Regulatory T Cells. J. Immunol. 173: 4433-4442 [Abstract] [Full Text]  
• Adams, S., O'Neill, D., Bhardwaj, N. (2004). Maturation Matters: Importance of Maturation for Antitumor Immunity of Dendritic Cell Vaccines. JCO 22: 3834-3835 [Full Text]  
• Park, S.-J., Nakagawa, T., Kitamura, H., Atsumi, T., Kamon, H., Sawa, S.-i., Kamimura, D., Ueda, N., Iwakura, Y., Ishihara, K., Murakami, M., Hirano, T. (2004). IL-6 Regulates In Vivo Dendritic Cell Differentiation through STAT3 Activation. J. Immunol. 173: 3844-3854 [Abstract] [Full Text]  
• Mailliard, R. B., Wankowicz-Kalinska, A., Cai, Q., Wesa, A., Hilkens, C. M., Kapsenberg, M. L., Kirkwood, J. M., Storkus, W. J., Kalinski, P. (2004). {alpha}-Type-1 Polarized Dendritic Cells: A Novel Immunization Tool with Optimized CTL-inducing Activity. Cancer Res. 64: 5934-5937 [Abstract] [Full Text]  
• Epardaud, M., Bonneau, M., Payot, F., Cordier, C., Megret, J., Howard, C., Schwartz-Cornil, I. (2004). Enrichment for a CD26hi SIRP- subset in lymph dendritic cells from the upper aero-digestive tract. J. Leukoc. Biol. 76: 553-561 [Abstract] [Full Text]  
• Chen, X., Doffek, K., Sugg, S. L., Shilyansky, J. (2004). Phosphatidylserine Regulates the Maturation of Human Dendritic Cells. J. Immunol. 173: 2985-2994 [Abstract] [Full Text]  
• Cignetti, A., Vallario, A., Roato, I., Circosta, P., Allione, B., Casorzo, L., Ghia, P., Caligaris-Cappio, F. (2004). Leukemia-Derived Immature Dendritic Cells Differentiate into Functionally Competent Mature Dendritic Cells That Efficiently Stimulate T Cell Responses. J. Immunol. 173: 2855-2865 [Abstract] [Full Text]  
• Avigan, D., Vasir, B., Gong, J., Borges, V., Wu, Z., Uhl, L., Atkins, M., Mier, J., McDermott, D., Smith, T., Giallambardo, N., Stone, C., Schadt, K., Dolgoff, J., Tetreault, J.-C., Villarroel, M., Kufe, D. (2004). Fusion Cell Vaccination of Patients with Metastatic Breast and Renal Cancer Induces Immunological and Clinical Responses. Clin. Cancer Res. 10: 4699-4708 [Abstract] [Full Text]  
• Vigouroux, S., Yvon, E., Biagi, E., Brenner, M. K. (2004). Antigen-induced regulatory T cells. Blood 104: 26-33 [Abstract] [Full Text]  

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