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Th1-Th2-Treg Interactions
Abstract
arXiv:1003.1053v1 [q-bio.CB] 4 Mar 2010
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.
Keywords: Nonlinear dynamics, Regulatory T cells, Desensitization
4
reference dose) is given by 4. Successful Therapy
1
T
stable manifold
Tr 0.01
100
1 10−4
0.01 0 5 10 15 20 25 30
100
t
10−4 separatrix
100 1
T1 Tr
T2
1 T1
0.01 100
T2 0.01
5
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practice could be improved by optimizing this step. As
immunologists have not yet fully understood all the reg-
ulatory mechanisms playing a role in allergic diseases, we
are sure that our model will need further refinement. Nev-
ertheless, our investigations already provide general tools
to model immune reactions with interacting lymphocytes.
Once the immunological picture of T cell regulation is more
complete, we will be able to give a more adequate descrip-
tion of the real system. In particular, it would be inter-
esting to extend the model further by including recently
identified T cell subsets, such as Th17 cells, which are
found to play a role in allergic asthma (Oboki et al., 2008;
Schmidt-Weber et al., 2007).
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