Concepts in tolerance induction in the lung
Dale T. Umetsu, MD, PhD
Harvard Medical School, Children’s Hospital
Boston, MA, USA
Asthma and allergy are thought to develop as a result of an over-abundance of Th2 cells and/or a relative-lack of regulatory T cells. We have shown that asthma and allergy are regulated by a number of distinct CD4+ T cells that include antigen-specific Th1-like TRegs and Th2-like TRegs cells, as well as Natural Killer T (NKT) cells. Both Th1-like TRegs and Th2-like TRegs cells arise following antigen exposure and express Foxp3, and both can potently inhibit the development of allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma. In contrast, NKT cells appear to be antigen-nonspecific, but are able to greatly exacerbate the development of allergen-induced AHR. The specific mechanisms and interactions that link Th2, TRegs and NKT cells in the airways are not yet clear.