Induction and Inhibition of the Th2 Phenotype Spread: Implications for Childhood Asthma
نویسنده
چکیده
METHODS. To induce and characterize phenotype spread, BALB/c mice were first immunized by a series of subcutaneous injections of egg ovalbumin and then challenged intranasally with ovalbumin, ragweed, or both simultaneously. Mice were finally challenged intranasally with ragweed alone to assess allergic response (Th2-mediated lung inflammation, ragweed-specific immunoglobulin E). To study the effect of time interval between the first and second antigens, the above-described experiment was repeated with ragweed being given either simultaneously with ovalbumin or 8, 24, or 48 hours after ovalbumin challenge. To investigate the role of activated Th2 cells in the induction of phenotype spread, severe combined immunodeficient (SCID) mice received ovalbumin-specific Th2 cells and naive CD4 T cells intravenously and were initially challenged with ovalbumin and ragweed and then challenged later with ragweed and assessed for allergic response. To evaluate whether trafficking of naive CD4 T cells to bronchial lymph nodes is required for the induction of phenotype spread, these cells were labeled and treated with an inhibitor of chemotaxis before the adoptive transfer experiments in the SCID mice. The effect on phenotype spread of immunostimulatory sequence-oligodeoxynucleotide (ISS-ODN), a Toll-like receptor 9 (TLR9) agonist, was first assessed in BALB/c mice by using the protocol described above, with injection of ISS-ODN before intranasal ovalbumin and ragweed challenge. ISSODN was also tested in the SCID adoptive-transfer model to study its effect on trafficking to regional lymph nodes.
منابع مشابه
Induction and inhibition of the Th2 phenotype spread: implications for childhood asthma.
The interactions between genetic and environmental factors play a major role in the development of childhood asthma. We hypothesized that a pre-existing Th2/asthmatic response can promote Th2 responses to newly encountered Ags (i.e., phenotype spread). To test this hypothesis, we developed a mouse model in which the requirements for the induction and inhibition of phenotype spread to a clinical...
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