Determining control parameters for dendritic cell-cytotoxic T lymphocyte interaction

✍ Scribed by Burkhard Ludewig; Philippe Krebs; Tobias Junt; Helen Metters; Neville J. Ford; Roy M. Anderson; Gennady Bocharov

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 522 KB
• Volume: 34
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200425085

✦ Synopsis

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.