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*
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261; and Departments of
Cell Biology and Physiology, and
Surgery and Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261
Dendritic cells (DC) can readily capture Ag from dead and dying cells for presentation to MHC class I-restricted CTL. We now show by using a primate model that DC also acquire Ag from healthy cells, including other DC. Coculture assays showed that fluorescently labeled plasma membrane was rapidly and efficiently transferred between DC, and transfer of intracellular proteins was observed to a lesser extent. Acquisition of labeled plasma membrane and intracellular protein was cell contact-dependent and was primarily a function of immature DC, whereas both immature and CD40L-matured DC could serve as donors. Moreover, immature DC could acquire labeled plasma membrane and intracellular proteins from a wide range of hemopoietic cells, including macrophages, B cells, and activated T cells. Notably, macrophages, which readily phagocytose apoptotic bodies, were very inefficient at acquiring labeled plasma membrane and intracellular proteins from other live macrophages or DC. With live-cell imaging techniques, we demonstrate that individual DC physically extract plasma membrane from other DC, generating endocytic vesicles of up to 1 µm in diameter. Finally, DC but not macrophages acquired an endogenous melanoma Ag expressed by live DC and cross-presented Ag to MHC class I-restricted CTL, demonstrating the immunological relevance of our finding. These data show for the first time that DC readily acquire Ag from other live cells. We suggest that Ag acquisition from live cells may provide a novel mechanism whereby DC can present Ag in the absence of direct infection, and may serve to expand and regulate the immune response in vivo.
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L. A. Harshyne, M. I. Zimmer, S. C. Watkins, and S. M. Barratt-Boyes A Role for Class A Scavenger Receptor in Dendritic Cell Nibbling from Live Cells J. Immunol., March 1, 2003; 170(5): 2302 - 2309. [Abstract] [Full Text] [PDF]
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 E. B. Olasz, J. Linton, and S. I. Katz Soluble proteins and haptens on bone marrow-derived dendritic cells are presented to host CD4 T cells in an MHC-restricted manner Int. Immunol., May 1, 2002; 14(5): 493 - 502. [Abstract] [Full Text] [PDF]
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Y. Valdez, W. Mah, M. M. Winslow, L. Xu, P. Ling, and S. E. Townsend Major Histocompatibility Complex Class II Presentation of Cell-associated Antigen Is Mediated by CD8{alpha}+ Dendritic Cells In Vivo J. Exp. Med., March 11, 2002; 195(6): 683 - 694. [Abstract] [Full Text] [PDF]
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S. Koido, Y. Tanaka, D. Chen, D. Kufe, and J. Gong The Kinetics of In Vivo Priming of CD4 and CD8 T Cells by Dendritic/Tumor Fusion Cells in MUC1-Transgenic Mice J. Immunol., March 1, 2002; 168(5): 2111 - 2117. [Abstract] [Full Text] [PDF]
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X.-Q. Zhao, X.-L. Huang, P. Gupta, L. Borowski, Z. Fan, S. C. Watkins, E. K. Thomas, and C. R. Rinaldo Jr. Induction of Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+ and CD4+ T-Cell Reactivity by Dendritic Cells Loaded with HIV-1 X4-Infected Apoptotic Cells J. Virol., February 22, 2002; 76(6): 3007 - 3014. [Abstract] [Full Text] [PDF]
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G. Arrode, C. Boccaccio, J.-P. Abastado, and C. Davrinche Cross-Presentation of Human Cytomegalovirus pp65 (UL83) to CD8+ T Cells Is Regulated by Virus-Induced, Soluble-Mediator-Dependent Maturation of Dendritic Cells J. Virol., January 1, 2002; 76(1): 142 - 150. [Abstract] [Full Text] [PDF]
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 M. F. Lipscomb and B. J. Masten Dendritic Cells: Immune Regulators in Health and Disease Physiol Rev, January 1, 2002; 82(1): 97 - 130. [Abstract] [Full Text] [PDF]
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R. Kammerer, D. Stober, P. Riedl, C. Oehninger, R. Schirmbeck, and J. Reimann Noncovalent Association with Stress Protein Facilitates Cross-Priming of CD8+ T Cells to Tumor Cell Antigens by Dendritic Cells J. Immunol., January 1, 2002; 168(1): 108 - 117. [Abstract] [Full Text] [PDF]
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J. Colino, Y. Shen, and C. M. Snapper Dendritic Cells Pulsed with Intact Streptococcus pneumoniae Elicit both Protein- and Polysaccharide-specific Immunoglobulin Isotype Responses In Vivo through Distinct Mechanisms J. Exp. Med., December 31, 2001; 195(1): 1 - 14. [Abstract] [Full Text] [PDF]
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