Murine model of tolerance to adjuvant-driven allergen-specific immunotherapy

During the last years, we have established a murine model for allergic asthma tothe major cat allergenFel d 1 that we used to test CpG-based specific immunotherapy. We have shownthat the allergic response to Fel d 1 was significantly reduced in mice undergoing CpG-driven immunotherapy (manuscript in preparation). Unexpectedly, the secretion of TNF was observed in the broncho-alveolar lavages of the treated mice. The TNF-TNFR2 interaction plays a critical role in the generation, expansion and function of human and mouse Tregs[51]and defects in TNFR2 signaling have been found in many autoimmune disorders [52].However, so far, no TNF dependent mechanism has been described in allergy immunotherapy treatments, in which the accent is invariably stressed on the suppressor cytokines IL-10 and TGF-β[53]. On basis of the Fel d 1 SIT model, we aim to gain in understanding the pathwaysand networksinduced by CpG triggering and the role of TNF in the stimulation of (unconventional) Tregs.We will utilize TNFKO and TNFR2KO mouse strains, as well as conditional TNFKO miceand analyze various cellular types, measure various layers of ‘omics’ in sorted T cell subsets following the course of allergy induction and CpG treatment.