1. Mechanisms of Immune Sensitization in Food Allergy
Treatments to prevent or eliminate food allergy are virtually non-existent. Developing a robust murine model of food allergy would provide a powerful tool with which to test hypotheses regarding mechanisms of immunological sensitization to ingested antigens as well as allergic responses to foods. Using “knock-in” mice harboring an activated variant of the IL-4 receptor, we have recently characterized mice that serve this function perfectly, developing IgE responses following enteral allergen exposure and exhibiting intense anaphylactic reactions upon ingestion challenge. We are using this novel model along with a number of available mutant strains and blocking antibodies to examine the roles of IgE and mast cells in the induction of TH2 and Treg responses.
2. Immunobiology of Eczema Vaccinatum
Eczema vaccinatum (EV) is a severe, overwhelming infection to vaccinia virus, (the small pox vaccine) which can occur in patients with atopic dermatitis. Recent concerns regarding the potential use of small pox as a bioterror agent have led the National Institutes of Allergy and Infectious Diseases of the National Institutes of Health to convene a consortium of researchers to study the mechanisms whereby allergic inflammation of the skin predisposes to such an abnormal response to the virus. Using genetically-engineered mice with mutations that result in allergic skin inflammation (targeted null mutants of RelB or FoxP3) we have observed markedly impaired induction of effector cytolytic T cell responses to vaccinia virus when it is encountered via eczematous skin. Our current studies focus on the roles of the cytokines IL-10 and IL-17 in responses to vaccinia.