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Immune Tolerance

Concepts in tolerance induction in the lung

dale umetsu
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. 

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