  Regulatory T cells (Treg) have recently been identified as playing a central
role in allergy and during allergen-specific immunotherapy. We have extended
our previous mathematical model describing the nonlinear dynamics of Th1-Th2
regulation by including Treg cells and their major cytokines. We hypothesize
that immunotherapy mainly acts on the T cell level and that the decisive
process can be regarded as a dynamical phenomenon. The model consists of
nonlinear differential equations which describe the proliferation and mutual
suppression of different T cell subsets. The old version of the model was based
upon the Th1-Th2 paradigm and is successful in describing the "Th1-Th2 switch"
which was considered the decisive event during specific immunotherapy. In
recent years, however, the Th1-Th2 paradigm has been questioned and therefore,
we have investigated a modified model in order to account for the influence of
a regulatory T cell type. We examined the extended model by means of numerical
simulations and analytical methods. As the modified model is more complex, we
had to develop new methods to portray its characteristics. The concept of
stable manifolds of fixed points of a stroboscobic map turned out to be
especially important. We found that when including regulatory T cells, our
model can describe the events in allergen-specific immunotherapy more
accurately. Our results suggest that the decisive effect of immunotherapy, the
increased proliferation of Treg and suppression of Th2 cells, crucially depends
on the administration of high dose injections right before the maintenance
phase sets in. Empirical protocols could therefore be improved by optimizing
this step of therapy.
