The role of regulatory T cells in allergy

A dramatic increase in prevalence of allergy observed within the last two decades has been associated with better hygiene, increased use of antibiotics and improved vaccination. Infections are important for the induction of regulatory elements within the immune system, and it has been suggested that fewer infections have altered the generation of regulatory T cells (Tregs); a cell type that actively control or suppress the function of other T cells, including T-cell mediated allergic reactions. To get fur ther insight into the role of Tregs in allergy we will study children with cow's milk allergy. The disease is a limited duration (months) and it is therefore a unique clinical model to study tolerance induction. In a prospective study we will follow child ren with cow's milk allergy for over a year. This approach will enable examination of time-dependent changes in Treg function within each individual before and after tolerance develop, and compare these children with those that do not become tolerant. We have also established an experimental animal model of food allergy to study the suppressive effect of Tregs, their trafficking and interaction with other cell types more in detail. Treg-interactions with other cell types will also be studied in cells obta ined from allergic rhinitis patients. We have generated a mouse that is deficient for the receptor (pIgR KO) that transports secretory immunoglobulins to the luminal side of mucosal surfaces. Antigen feeding of these mice induced greater numbers of Tregs than wild type mice. Our aim is to identify the mechanisms by which these pIgR KO mice induce more functional Tregs. This effect will be investigated both in experimental models for food allergy and asthma. Our aim is to define the role that Tregs play i n allergic inflammation and understand how induction of Tregs is regulated. Treatment to enhance regulatory T-cell responses might be useful in prevention and treatment of allergic diseases.