1. Tolerance induction using novel antigen-coupled carriers in a model of allergic asthma (125.5)
- Author
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Charles Smarr, Woon Teck Yap, Derrick McCarthy, Paul Bryce, Lonnie Shea, and Stephen Miller
- Subjects
Immunology ,Immunology and Allergy - Abstract
Current immunotherapy for Th2-associated allergic disease is inefficient and has a significant risk of inducing anaphylaxis. There is significant need for new treatments to safely, efficiently induce antigen-specific tolerance in allergic disease. Antigen-coupled cells (Ag-SP) have been used by our lab to prevent and treat Th1/Th17-mediated models of autoimmune disease and, more recently, Th2-mediated models of allergic asthma and food allergy. Ag-SP treatment is currently entering a Phase II clinical trial in multiple sclerosis patients in Germany. Due to the technical complications of such treatment, however, we have begun to explore new antigen carriers for the induction of tolerance in autoimmune and allergic diseases. Initial work with antigen coupled to inert polystyrene and biodegradable PLGA microparticles (Ag-MP) identified these carriers as effective at inducing tolerance in EAE. We have extended these findings to a common ovalbumin (OVA)-alum induced mouse model of allergic asthma. Prophylactically, OVA- MP induce protective tolerance - inhibiting production of OVA-specific IgE antibodies and lung inflammation and preventing OVA-specific proliferation and Th2 cytokine production by restimulated lymphocytes. Given post-sensitization, OVA-MP inhibit Th2 responses in restimulation cultures but do not, in the short frame examined, inhibit other parameters of disease. This work identifies Ag-MP as promising inducers of tolerance for allergic disease.
- Published
- 2012