Changing paradigms in the immunological science of allergy

The nonallergic roles of mast cells in infections and immune tolerance recently have been elucidated more fully at mechanistic levels. Mast cells that have been activated by contact with microbial surfaces secrete chemotactic mediators capable of attracting leukocytes through blood vessels permeabilized by other mediators. In the setting of allograft transplantation, regulatory CD4 T cells promote tolerance both by direct immunosuppressive effects and by releasing interleukin (IL)-9 that attracts and stimulates differentiation of mast cells with the capacity to induce local tolerance. For the first time in over 20 years, two new subclasses of CD4 T cells have been identified that have major immune functions. The first are T-helper interleukin-17 (T(H)17) cells, which mediate acute and chronic inflammation in recurring exacerbations of autoimmune diseases, and the second are sets of adaptive regulatory T cells, which control CD4 effector T cells and other immune effector cells by secreting transforming growth factor-beta or IL-10.