The efficacy of immunotherapy in an experimental murine model of allergic asthma is related to the strength and site 1 of T cell activation during immunotherapy

In the present study, the relation between the efficacy of immunotherapy, a nd the strength and site of T cell activation during immunotherapy was eval uated. We used a model of allergic asthma in which OVA-sensitized and OVA-c hallenged mice display increased airway hyperresponsiveness, airway inflamm ation, and Th2 cytokine production by OVA-specific T cells. In this model, different immunotherapy strategies, including different routes of administr ation, or treatment with entire OVA or the immunodominant T cell epitope OV A(323-339), or treatment with a peptide analogue of OVA(323-339) with alter ed T cell activation capacity were studied. To gain more insight in how imm unotherapy affects allergen-specific T cells, the site of Ag-specific T cel l activation and the magnitude of the T cell response induced during differ ent immunotherapy strategies were determined using an adoptive transfer mod el. Our data suggest that amelioration of airway hyperresponsiveness and in flammation is associated with the induction of a strong, synchronized, and systemic T cell response, resulting in a decreased OVA-specific Th2 respons e. In contrast, deterioration of the disease after Immunotherapy is associa ted with the induction of a weak nonsynchronized T cell response, resulting in the enhancement of the OVA-specific Th2 response after challenge.