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Regulatory T cells (Treg) have recently been identified as playing a centralrole in allergy and during allergen-specific immunotherapy. We have extendedour previous mathematical model describing the nonlinear dynamics of Th1-Th2regulation by including Treg cells and their major cytokines. We hypothesizethat immunotherapy mainly acts on the T cell level and that the decisiveprocess can be regarded as a dynamical phenomenon. The model consists ofnonlinear differential equations which describe the proliferation and mutualsuppression of different T cell subsets. The old version of the model was basedupon the Th1-Th2 paradigm and is successful in describing the "Th1-Th2 switch"which was considered the decisive event during specific immunotherapy. Inrecent years, however, the Th1-Th2 paradigm has been questioned and therefore,we have investigated a modified model in order to account for the influence ofa regulatory T cell type. We examined the extended model by means of numericalsimulations and analytical methods. As the modified model is more complex, wehad to develop new methods to portray its characteristics. The concept ofstable manifolds of fixed points of a stroboscobic map turned out to beespecially important. We found that when including regulatory T cells, ourmodel can describe the events in allergen-specific immunotherapy moreaccurately. Our results suggest that the decisive effect of immunotherapy, theincreased proliferation of Treg and suppression of Th2 cells, crucially dependson the administration of high dose injections right before the maintenancephase sets in. Empirical protocols could therefore be improved by optimizingthis step of therapy.

Mathematical Modelling of Allergy and Specific Immunotherapy: Th1-Th2-Treg Interactions