1. Regulation of Immune Responses by IgE Antibodies

Allergic individuals produce large amounts of IgE antibodies. These circulate in the blood and are present in the lungs, gastrointestinal tract, skin and other organs where they are bound to IgE receptors on mast cells. Some IgE antibodies specifically recognize allergens, including airborne particles (pollens, animal danders, etc.), foods, insect venoms and drugs. The presence of such allergen-specific IgE's can be determined by skin testing or blood tests.

Allergic reactions are triggered when mast cell-bound IgE encounters specific allergens, leading to receptor aggregation, mast cell activation and the release of mediators, including histamine, prostoglandins, leukotrienes and cytokines. The antigen-driven cross-linking of mast cell-bound IgE is the inciting event in acute asthma attacks or anaphylaxis.

We and others have recently observed that IgE antibodies can also exert effects on many other aspects of the immune response. We aim to define the biological effects of monomeric IgE and understand their implications for allergic pathogenesis.

2. Immunobiology of Eczema Vaccinatum

Eczema vaccinatum (EV) is a severe, overwhelming infection to the vaccine strain, vaccinia virus, contained in small pox vaccine which can occur in patients with eczema (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.

3. Basophils in Early Responses to Allergens

IgE production and tissue inflammation in allergic individuals is driven by the cytokine, IL-4. IL-4 is produced by Th2 T helper cells present at allergic sites. The expansion of Th2 cells during allergic responses is IL-4 driven itself raising a ?chicken and egg? dilemma of where the first IL-4 comes from in allergic tissues. We have recently observed that a rare circulating leukocyte, the basophil, is rapidly recruited immediately following allergen exposure and produces abundant IL-4. We are now testing whether IL-4 producing basophils are the key instigators of Th2-driven allergic responses following mold inhalation in a mouse asthma model.