The Efficacy of Immunotherapy in an Experimental Murine Model of Allergic Asthma Is Related to the Strength and Site of T Cell Activation During Immunotherapy

Abstract

In the present study, the relation between the efficacy of immunotherapy, and the strength and site of T cell activation during immunotherapy was evaluated. We used a model of allergic asthma in which OVA-sensitized and OVA-challenged mice display increased airway hyperresponsiveness, airway inflammation, and Th2 cytokine production by OVA-specific T cells. In this model, different immunotherapy strategies, including different routes of administration, or treatment with entire OVA or the immunodominant T cell epitope OVA323–339, or treatment with a peptide analogue of OVA323–339 with altered T cell activation capacity were studied. To gain more insight in how immunotherapy affects allergen-specific T cells, the site of Ag-specific T cell activation and the magnitude of the T cell response induced during different immunotherapy strategies were determined using an adoptive transfer model. Our data suggest that amelioration of airway hyperresponsiveness and inflammation is associated with the induction of a strong, synchronized, and systemic T cell response, resulting in a decreased OVA-specific Th2 response. In contrast, deterioration of the disease after immunotherapy is associated with the induction of a weak nonsynchronized T cell response, resulting in the enhancement of the OVA-specific Th2 response after challenge.

CD4+CD25+ T cell depletion impairs tolerance induction in a murine model of asthma

“…T cell hyporesponsiveness in our model was a relatively late phenomenon (day 52). We know that, during the phase of tolerance induction, T cells undergo first a period of intense activation [15, 28]. Our observations are in agreement with this concept as BLN cells from OVA INT mice proliferated indeed more strongly than PBS INT mice at day 43 (6 days after INT) (Fig.…”

Development of a human mitochondria-focused cDNA microarray (hMitChip) and validation in skeletal muscle cells: implications for pharmaco- and mitogenomics

“…38 Of interest is also the observed change in the expression of AK1, which is involved in nucleotide/ATP synthesis and is essential for muscle cellular energetics and performance. 39 The attenuated expression of genes involved in the degradation of medium and very long chain fatty acids (ACADM and ACADVL, respectively) is also concordant with previous reports on similar effects of glucocorticoids on liver fatty acid metabolism. 40 In contrast, genes like ACADC (also related to lipid degradation) and FACL2 (involved in lipid synthesis) were induced by Dex.…”

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma

“…Also, in murine models, IT has shown effects on the development of airway inflammation and airway hyperresponsiveness (AHR) (24)(25)(26)(27). However, in most of the studies, IT was performed prior to first allergen challenge, and the effect of IT on already established airway disease is less well understood.…”