Determining control parameters for dendritic cell-cytotoxic T lymphocyte interaction

Hdl Handle:
http://hdl.handle.net/10034/70437
Title:
Determining control parameters for dendritic cell-cytotoxic T lymphocyte interaction
Authors:
Ludewig, Burkhard; Krebs, Philippe; Junt, Tobias; Metters, Helen; Ford, Neville J.; Anderson, Roy M.; Bocharov, Gennady
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.
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
Citation:
European Journal of Immunology, 2004, 34(9), pp. 2407-2418
Publisher:
WILEY-VCH Verlag GmbH & Co. KGaA
Journal:
European Journal of Immunology
Publication Date:
2004
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.
Appears in Collections:
Mathematics

Full metadata record

DC FieldValue Language
dc.contributor.authorLudewig, Burkharden
dc.contributor.authorKrebs, Philippeen
dc.contributor.authorJunt, Tobiasen
dc.contributor.authorMetters, Helenen
dc.contributor.authorFord, Neville J.en
dc.contributor.authorAnderson, Roy M.en
dc.contributor.authorBocharov, Gennadyen
dc.date.accessioned2009-06-15T11:29:43Zen
dc.date.available2009-06-15T11:29:43Zen
dc.date.issued2004en
dc.identifier.citationEuropean Journal of Immunology, 2004, 34(9), pp. 2407-2418en
dc.identifier.issn0014-2980en
dc.identifier.issn1521-4141en
dc.identifier.doi10.1002/eji.200425085en
dc.identifier.urihttp://hdl.handle.net/10034/70437en
dc.descriptionThis article is not available through ChesterRep.en
dc.description.abstractDendritic 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.en
dc.description.sponsorshipThis article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.en
dc.language.isoenen
dc.publisherWILEY-VCH Verlag GmbH & Co. KGaAen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/25061/homeen
dc.subjectCTLen
dc.subjectdendritic cellsen
dc.subjectvaccinationen
dc.subjecttumor immunityen
dc.titleDetermining control parameters for dendritic cell-cytotoxic T lymphocyte interactionen
dc.typeArticleen
dc.contributor.departmentUniversity 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 Sciencesen
dc.identifier.journalEuropean Journal of Immunologyen
All Items in ChesterRep are protected by copyright, with all rights reserved, unless otherwise indicated.