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CUTTING EDGE |
Departments of
*
Microbiology and
Surgery, Dartmouth Medical School, Lebanon, NH, 03756;
Immunex Corporation, Seattle, WA, 98101; and
§
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
A critical role for CD40/CD154 interactions in the generation of protective cell-mediated tumor immunity has been demonstrated previously. Herein, we show that the failure to generate systemic tumor immunity in the absence of CD40/CD154 interactions correlates with an inhibition of Th1-type cytokine production following tumor vaccination. Furthermore, protective antitumor responses can be restored in CD40-deficient mice by the coadministration of CD40+/+ but not CD40-/- dendritic cells (DCs) with tumor Ag, suggesting that CD40 is critical for the maturation and function of DCs in vivo. Finally, we demonstrate that an IL-12-transduced but not a mock-transduced tumor vaccine induces systemic tumor immunity in anti-CD154-treated and CD154-deficient mice. These data suggest that impaired antitumor responses in the absence of CD40/CD154 interactions are the result of a lesion in APC function, namely IL-12 production, and that CD40 plays a critical role in the maturation of DCs in vivo.
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K. Peggs, S. Verfuerth, and S. Mackinnon Induction of cytomegalovirus (CMV)-specific T-cell responses using dendritic cells pulsed with CMV antigen: a novel culture system free of live CMV virions Blood, February 15, 2001; 97(4): 994 - 1000. [Abstract] [Full Text] [PDF]
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M. Schnurr, F. Then, P. Galambos, C. Scholz, B. Siegmund, S. Endres, and A. Eigler Extracellular ATP and TNF-{alpha} Synergize in the Activation and Maturation of Human Dendritic Cells J. Immunol., October 15, 2000; 165(8): 4704 - 4709. [Abstract] [Full Text] [PDF]
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A. De Creus, K. Van Beneden, T. Taghon, F. Stolz, V. Debacker, J. Plum, and G. Leclercq Langerhans Cells That Have Matured In Vivo in the Absence of T Cells Are Fully Capable of Inducing a Helper CD4 as Well as a Cytotoxic CD8 Response J. Immunol., July 15, 2000; 165(2): 645 - 653. [Abstract] [Full Text] [PDF]
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P. Terheyden, P. t. Straten, E.-B. Brocker, E. Kampgen, and J. C. Becker CD40-Ligated Dendritic Cells Effectively Expand Melanoma-Specific CD8+ CTLs and CD4+ IFN-{gamma}-Producing T Cells from Tumor-Infiltrating Lymphocytes J. Immunol., June 15, 2000; 164(12): 6633 - 6639. [Abstract] [Full Text] [PDF]
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S. Muerkoster, J. D. Laman, M. Rocha, V. Umansky, and V. Schirrmacher Functional and in Situ Evidence for Nitric Oxide Production Driven by CD40-CD40L Interactions in Graft-versus-Leukemia Reactivity Clin. Cancer Res., May 1, 2000; 6(5): 1988 - 1996. [Abstract] [Full Text] [PDF]
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S. Skov, M. Bonyhadi, N. Odum, and J. A. Ledbetter IL-2 and IL-15 Regulate CD154 Expression on Activated CD4 T Cells J. Immunol., April 1, 2000; 164(7): 3500 - 3505. [Abstract] [Full Text] [PDF]
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C. N. Baxevanis, I. F. Voutsas, O. E. Tsitsilonis, A. D. Gritzapis, R. Sotiriadou, and M. Papamichail Tumor-Specific CD4+ T Lymphocytes from Cancer Patients Are Required for Optimal Induction of Cytotoxic T Cells Against the Autologous Tumor J. Immunol., April 1, 2000; 164(7): 3902 - 3912. [Abstract] [Full Text] [PDF]
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R. Josien, H.-L. Li, E. Ingulli, S. Sarma, B. R.Wong, M. Vologodskaia, R. M. Steinman, and Y. Choi Trance, a Tumor Necrosis Factor Family Member, Enhances the Longevity and Adjuvant Properties of Dendritic Cells in Vivo J. Exp. Med., February 7, 2000; 191(3): 495 - 502. [Abstract] [Full Text] [PDF]
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S. Schnell, J. W. Young, A. N. Houghton, and M. Sadelain Retrovirally Transduced Mouse Dendritic Cells Require CD4+ T Cell Help to Elicit Antitumor Immunity: Implications for the Clinical Use of Dendritic Cells J. Immunol., February 1, 2000; 164(3): 1243 - 1250. [Abstract] [Full Text] [PDF]
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S. M. Kiertscher, J. Luo, S. M. Dubinett, and M. D. Roth Tumors Promote Altered Maturation and Early Apoptosis of Monocyte-Derived Dendritic Cells J. Immunol., February 1, 2000; 164(3): 1269 - 1276. [Abstract] [Full Text] [PDF]
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P. A. Taylor, A. Panoskaltsis-Mortari, R. J. Noelle, and B. R. Blazar Analysis of the Requirements for the Induction of CD4+ T Cell Alloantigen Hyporesponsiveness by Ex Vivo Anti-CD40 Ligand Antibody J. Immunol., January 15, 2000; 164(2): 612 - 622. [Abstract] [Full Text] [PDF]
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L. Lefrancois, J. D. Altman, K. Williams, and S. Olson Soluble Antigen and CD40 Triggering Are Sufficient to Induce Primary and Memory Cytotoxic T Cells J. Immunol., January 15, 2000; 164(2): 725 - 732. [Abstract] [Full Text] [PDF]
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M. E. Ozaki, B. A. Coren, T. N. Huynh, D. J. Redondo, H. Kikutani, and S. R. Webb CD4+ T Cell Responses to CD40-Deficient APCs: Defects in Proliferation and Negative Selection Apply Only with B Cells as APCs J. Immunol., November 15, 1999; 163(10): 5250 - 5256. [Abstract] [Full Text] [PDF]
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M. Subklewe, A. Chahroudi, A. Schmaljohn, M. G. Kurilla, N. Bhardwaj, and R. M. Steinman Induction of Epstein-Barr Virus-Specific Cytotoxic T-Lymphocyte Responses Using Dendritic Cells Pulsed With EBNA-3A Peptides or UV-Inactivated, Recombinant EBNA-3A Vaccinia Virus Blood, August 15, 1999; 94(4): 1372 - 1381. [Abstract] [Full Text] [PDF]
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I. F. Hermans, D. S. Ritchie, A. Daish, J. Yang, M. R. Kehry, and F. Ronchese Impaired Ability of MHC Class II-/- Dendritic Cells to Provide Tumor Protection is Rescued by CD40 Ligation J. Immunol., July 1, 1999; 163(1): 77 - 81. [Abstract] [Full Text] [PDF]
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J. E. Buhlmann, M. Gonzalez, B. Ginther, A. Panoskaltsis-Mortari, B. R. Blazar, D. L. Greiner, A. A. Rossini, R. Flavell, and R. J. Noelle Cutting Edge: Sustained Expansion of CD8+ T Cells Requires CD154 Expression by Th Cells in Acute Graft Versus Host Disease J. Immunol., April 15, 1999; 162(8): 4373 - 4376. [Abstract] [Full Text] [PDF]
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R. E.M. Toes, F. Ossendorp, R. Offringa, and C. J.M. Melief CD4 T Cells and Their Role in Antitumor Immune Responses J. Exp. Med., March 1, 1999; 189(5): 753 - 756. [Full Text] [PDF]
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C.G. Begley and N.A. Nicola Resolving Conflicting Signals: Cross Inhibition of Cytokine Signaling Pathways Blood, March 1, 1999; 93(5): 1443 - 1447. [Full Text] [PDF]
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