Dendritic cells (DCs) have the capacity to initiate immune responses, but it has been postulated that they may also be involved in inducing peripheral tolerance. To examine the function of DCs in the steady state we devised an antigen delivery system targeting these specialized antigen presenting cells in vivo using a monoclonal antibody to a DC-restricted endocytic receptor, DEC-205. Our experiments show that this route of antigen delivery to DCs is several orders of magnitude more efficient than free peptide in complete Freund's adjuvant (CFA) in inducing T cell activation and cell division. However, T cells activated by antigen delivered to DCs are not polarized to produce T helper type 1 cytokine interferon γ and the activation response is not sustained. Within 7 d the number of antigen-specific T cells is severely reduced, and the residual T cells become unresponsive to systemic challenge with antigen in CFA. Coinjection of the DC-targeted antigen and anti-CD40 agonistic antibody changes the outcome from tolerance to prolonged T cell activation and immunity. We conclude that in the absence of additional stimuli DCs induce transient antigen-specific T cell activation followed by T cell deletion and unresponsiveness.
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17 September 2001
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September 17 2001
Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo
Daniel Hawiger,
Daniel Hawiger
aLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021
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Kayo Inaba,
Kayo Inaba
cLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
eLaboratory of Immunobiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
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Yair Dorsett,
Yair Dorsett
aLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021
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Ming Guo,
Ming Guo
aLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021
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Karsten Mahnke,
Karsten Mahnke
cLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
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Miguel Rivera,
Miguel Rivera
cLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
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Jeffrey V. Ravetch,
Jeffrey V. Ravetch
dLaboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10021
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Ralph M. Steinman,
Ralph M. Steinman
cLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
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Michel C. Nussenzweig
Michel C. Nussenzweig
aLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021
bHoward Hughes Medical Institute, The Rockefeller University, New York, NY 10021
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Daniel Hawiger
aLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021
Kayo Inaba
cLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
eLaboratory of Immunobiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
Yair Dorsett
aLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021
Ming Guo
aLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021
Karsten Mahnke
cLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
Miguel Rivera
cLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
Jeffrey V. Ravetch
dLaboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10021
Ralph M. Steinman
cLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
Michel C. Nussenzweig
aLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021
bHoward Hughes Medical Institute, The Rockefeller University, New York, NY 10021
Abbreviations used in this paper: CFSE, 5-(6)-carboxyfluorescein diacetate succinimidyl diester; DC, dendritic cell; HEL, hen egg lysozyme; MMR, macrophage mannose receptor.
Received:
June 26 2001
Revision Requested:
August 02 2001
Accepted:
August 10 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Exp Med (2001) 194 (6): 769–780.
Article history
Received:
June 26 2001
Revision Requested:
August 02 2001
Accepted:
August 10 2001
Citation
Daniel Hawiger, Kayo Inaba, Yair Dorsett, Ming Guo, Karsten Mahnke, Miguel Rivera, Jeffrey V. Ravetch, Ralph M. Steinman, Michel C. Nussenzweig; Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo. J Exp Med 17 September 2001; 194 (6): 769–780. doi: https://doi.org/10.1084/jem.194.6.769
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