Plasmacytoid dendritic cells downregulate the allergen induced T cell proliferation in a human in vitro allergy model

The description of complex regulatory immunologic pathways represents a major difficulty during preclinical testing. Animal models are widely used for this purpose. In the study described herein, a human in vitro allergy model was established providing an alternative method to investigate allergy driven immune responses. The model should be able to show the influence of cellular components as i.e. plasmacytoid dendritic cells (pDC) or drug candidates. This might allow the avoidance of animal experiments and relates more closely to the human situation. For example, plasmacytoid dendritic cells (pDC) representing a DC subpopulation with major immunologic regulatory functions, were investigated to show a clear analogy to the in vivo situation in the model.

An allergen-specific T cell immune response can reproducibly be performed using the human in vitro allergy model. The presence of pDC in this model clearly reduced the allergen-induced immune response, demonstrating the regulatory properties of this DC subpopulation depending on the stimulatory APC to pDC cell ratio. Hence, this model enables to mimic allergen-specific immune responses and furthermore regulatory mechanisms. In the future, this model thus might be applicable for efficacy testing of potential immunoregulatory cellular therapeutics or biomolecules with the advantages of avoiding animal experiments and enabling greater predictivity for the human situation.