Allergic diseases result from an unbalanced response of the specific immune system, generating allergen-specific IgE antibodies, which mediate various clinical symptoms, such as immediate type hypersensitivity. The disease severity correlates with the activity of CD4+ T cells.
The existence of allergen-specific CD4+ Th2 cells, however, is not sufficient for allergy pathogenesis, since these cells are also found in healthy individuals. In contrast, allergen specific regulatory T cells (Tregs) occur at higher frequency than their effector counterparts in healthy individuals and are capable of suppressing proliferation and cytokine expression of Th1 and Th2 cells.
Tregs are defined on the basis of their function, in contrast to Th1 or Th2 cells, which are characterized by their gene products. The exact definition of the Tregs phenotype is therefore often difficult. Recent evidence revealed that also CD8+ Tregs contribute to peripheral tolerance.
However the contribution of these cells in allergic disease is unclear. We have preliminary evidence showing that CD8+ T cells play an important role in the allergen-specific responses. Aim of the proposal is to analyze the contribution of allergen-specific CD8+ T cells to the tolerance against allergens in healthy and allergic individuals.
Therefore the impact of allergen-specific, effector versus regulatory CD8+ T cells in allergen-driven immune reactions will be investigated along with their crosstalk to CD4 subsets and the antigen presenting cells.
We anticipate an advanced understanding of the cellular players in tolerance and pathogenesis of allergy and in turn new approaches in anti-allergic therapy.
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