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    Determining control parameters for dendritic cell-cytotoxic T lymphocyte interaction

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    Authors
    Ludewig, Burkhard
    Krebs, Philippe
    Junt, Tobias
    Metters, Helen
    Ford, Neville J.
    Anderson, Roy M.
    Bocharov, Gennady
    Affiliation
    University of Zürich ; University of Zürich ; University of Zürich ; University of Zürich ; University College Chester ; Imperial College, University of London ; Institute of Numerical Mathematics, Russian Academy of Sciences
    Publication Date
    2004-08-05
    
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    Abstract
    Dendritic cells (DC) are potent immunostimulatory cells facilitating antigen transport to lymphoid tissues and providing efficient stimulation of T cells. A series of experimental studies in mice demonstrated that cytotoxic T lymphocytes (CTL) can be efficiently induced by adoptive transfer of antigen-presenting DC. However, the success of DC-based immunotherapeutic treatment of human cancer, for example, is still limited because the details of the regulation and kinetics of the DC-CTL interaction are not yet completely understood. Using a combination of experimental mouse studies, mathematical modeling, and nonlinear parameter estimation, we analyzed the population dynamics of DC-induced CTL responses. The model integrates a predator-prey-type interaction of DC and CTL with the non-linear compartmental dynamics of T cells. We found that T cell receptor avidity, the half-life of DC, and the rate of CTL-mediated DC-elimination are the major control parameters for optimal DC-induced CTL responses. For induction of high avidity CTL, the number of adoptively transferred DC was of minor importance once a minimal threshold of approximately 200 cells per spleen had been reached. Taken together, our study indicates that the availability of high avidity T cells in the recipient in combination with the optimal application regimen is of prime importance for successful DC-based immunotherapy.
    Citation
    European Journal of Immunology, 2004, 34(9), pp. 2407-2418
    Publisher
    WILEY-VCH Verlag GmbH & Co. KGaA
    Journal
    European Journal of Immunology
    URI
    http://hdl.handle.net/10034/70437
    DOI
    10.1002/eji.200425085
    Additional Links
    http://www3.interscience.wiley.com/journal/25061/home
    Type
    Article
    Language
    en
    Description
    This article is not available through ChesterRep.
    ISSN
    0014-2980
    1521-4141
    Sponsors
    This article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.
    ae974a485f413a2113503eed53cd6c53
    10.1002/eji.200425085
    Scopus Count
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    Mathematics

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