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Malaghan Institute of Medical Research, Wellington School of Medicine, Wellington, New Zealand
The fate of dendritic cells (DC) after they have initiated a T cell
immune response is still undefined. We have monitored the migration of
DC labeled with a fluorescent tracer and injected s.c. into naive mice
or into mice with an ongoing immune response. DC not loaded with Ag
were detected in the draining lymph node in excess of 7 days after
injection with maximum numbers detectable 
40 h after transfer. In
contrast, DC that had been loaded with an MHC class I-binding peptide
disappeared from the lymph node with kinetics that parallel the known
kinetics of activation of CD8+ T cells to effector
function. In the presence of high numbers of specific CTL precursors,
as in TCR transgenic mice, DC numbers were significantly decreased by
72 h after injection. The rate of DC disappearance was extremely
rapid and efficient in recently immunized mice and was slower in
"memory" mice in which memory CD8+ cells needed to
reacquire effector function before mediating DC elimination. We also
show that CTL-mediated clearance of Ag-loaded DC has a notable effect
on immune responses in vivo. Ag-specific CD8+ T cells
failed to divide in response to Ag presented on a DC if the DC were
targets of a pre-existing CTL response. The induction of antitumor
immunity by tumor Ag-loaded DC was also impaired. Therefore,
CTL-mediated clearance of Ag-loaded DC may serve as a negative feedback
mechanism to limit the activity of DC within the lymph
node.
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B. Wang, H. Chen, X. Jiang, M. Zhang, T. Wan, N. Li, X. Zhou, Y. Wu, F. Yang, Y. Yu, et al. Identification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein Blood, July 1, 2004; 104(1): 200 - 206. [Abstract] [Full Text] [PDF]
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H. Matsuyoshi, S. Senju, S. Hirata, Y. Yoshitake, Y. Uemura, and Y. Nishimura 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., January 15, 2004; 172(2): 776 - 786. [Abstract] [Full Text] [PDF]
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A. Martin-Fontecha, S. Sebastiani, U. E. Hopken, M. Uguccioni, M. Lipp, A. Lanzavecchia, and F. Sallusto Regulation of Dendritic Cell Migration to the Draining Lymph Node: Impact on T Lymphocyte Traffic and Priming J. Exp. Med., August 18, 2003; 198(4): 615 - 621. [Abstract] [Full Text] [PDF]
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M. Leverkus, A. D. McLellan, M. Heldmann, A. O. Eggert, E.-B. Brocker, N. Koch, and E. Kampgen MHC class II-mediated apoptosis in dendritic cells: a role for membrane-associated and mitochondrial signaling pathways Int. Immunol., August 1, 2003; 15(8): 993 - 1006. [Abstract] [Full Text] [PDF]
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J. C. R. Hafalla, A. Morrot, G.-i. Sano, G. Milon, J. J. Lafaille, and F. Zavala Early Self-Regulatory Mechanisms Control the Magnitude of CD8+ T Cell Responses Against Liver Stages of Murine Malaria J. Immunol., July 15, 2003; 171(2): 964 - 970. [Abstract] [Full Text] [PDF]
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I. Hwang, X. Shen, and J. Sprent Direct stimulation of naive T cells by membrane vesicles from antigen-presenting cells: Distinct roles for CD54 and B7 molecules PNAS, May 27, 2003; 100(11): 6670 - 6675. [Abstract] [Full Text] [PDF]
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C. E. Hirst, M. S. Buzza, C. H. Bird, H. S. Warren, P. U. Cameron, M. Zhang, P. G. Ashton-Rickardt, and P. I. Bird The Intracellular Granzyme B Inhibitor, Proteinase Inhibitor 9, Is Up-Regulated During Accessory Cell Maturation and Effector Cell Degranulation, and Its Overexpression Enhances CTL Potency J. Immunol., January 15, 2003; 170(2): 805 - 815. [Abstract] [Full Text] [PDF]
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A. Nopora and T. Brocker Bcl-2 Controls Dendritic Cell Longevity In Vivo J. Immunol., September 15, 2002; 169(6): 3006 - 3014. [Abstract] [Full Text] [PDF]
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M. C. Wolkers, M. Toebes, M. Okabe, J. B. A. G. Haanen, and T. N. M. Schumacher Optimizing the Efficacy of Epitope-Directed DNA Vaccination J. Immunol., May 15, 2002; 168(10): 4998 - 5004. [Abstract] [Full Text] [PDF]
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M. J. Palmowski, E. M.-L. Choi, I. F. Hermans, S. C. Gilbert, J.-L. Chen, U. Gileadi, M. Salio, A. Van Pel, S. Man, E. Bonin, et al. Competition Between CTL Narrows the Immune Response Induced by Prime-Boost Vaccination Protocols J. Immunol., May 1, 2002; 168(9): 4391 - 4398. [Abstract] [Full Text] [PDF]
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H. P. Jones, L. Tabor, X. Sun, M. D. Woolard, and J. W. Simecka Depletion of CD8+ T Cells Exacerbates CD4+ Th Cell-Associated Inflammatory Lesions During Murine Mycoplasma Respiratory Disease J. Immunol., April 1, 2002; 168(7): 3493 - 3501. [Abstract] [Full Text] [PDF]
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S. Gardella, C. Andrei, L. V. Lotti, A. Poggi, M. R. Torrisi, M. R. Zocchi, and A. Rubartelli CD8+ T lymphocytes induce polarized exocytosis of secretory lysosomes by dendritic cells with release of interleukin-1{beta} and cathepsin D Blood, October 1, 2001; 98(7): 2152 - 2159. [Abstract] [Full Text] [PDF]
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J. P. Medema, D. H. Schuurhuis, D. Rea, J. van Tongeren, J. de Jong, S. A. Bres, S. Laban, R. E.M. Toes, M. Toebes, T. N.M. Schumacher, et al. Expression of the Serpin Serine Protease Inhibitor 6 Protects Dendritic Cells from Cytotoxic T Lymphocyte-Induced Apoptosis: Differential Modulation by T Helper Type 1 and Type 2 Cells J. Exp. Med., September 3, 2001; 194(5): 657 - 668. [Abstract] [Full Text] [PDF]
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F. Ronchese and I. F. Hermans Killing of Dendritic Cells: A Life Cut Short or a Purposeful Death? J. Exp. Med., September 3, 2001; 194(5): f23 - f26. [Full Text] [PDF]
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O. T. M. Chan, V. Paliwal, J. M. McNiff, S.-H. Park, A. Bendelac, and M. J. Shlomchik Deficiency in {beta}2-Microglobulin, But Not CD1, Accelerates Spontaneous Lupus Skin Disease While Inhibiting Nephritis in MRL-Faslpr Mice: An Example of Disease Regulation at the Organ Level J. Immunol., September 1, 2001; 167(5): 2985 - 2990. [Abstract] [Full Text] [PDF]
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D. J. Nelson, S. Mukherjee, C. Bundell, S. Fisher, D. van Hagen, and B. Robinson Tumor Progression Despite Efficient Tumor Antigen Cross-Presentation and Effective "Arming" of Tumor Antigen-Specific CTL J. Immunol., May 1, 2001; 166(9): 5557 - 5566. [Abstract] [Full Text] [PDF]
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S. Corinti, C. Albanesi, A. la Sala, S. Pastore, and G. Girolomoni Regulatory Activity of Autocrine IL-10 on Dendritic Cell Functions J. Immunol., April 1, 2001; 166(7): 4312 - 4318. [Abstract] [Full Text] [PDF]
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