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*
Mayo Clinic, Department of Immunology, Rochester, MN 55902; and
Novartis Horsham Research Centre, Horsham, United Kingdom
IL-5 production in vivo plays a unique role in the production,
activation, and localization of eosinophils in a variety of allergic
conditions. The current paradigm suggests that allergen-specific Th2
cells are the main source for the IL-5 production. The experiments
outlined in this work, however, suggest that in vivo production of IL-5
by NK cells can separately influence eosinophil-associated inflammatory
responses. Specifically, a mouse model of allergic inflammation was
used in which C57BL/6 mice were immunized and challenged with a short
ragweed Ag extract, known to induce a selective eosinophilia within the
peritoneal cavity. Peritoneal lavage fluids from these mice also
contained increased numbers of T cells and NK cells, as well as
significantly elevated levels of IL-4, IL-5, and IFN-
.
Flow-cytometric analysis of cytokine-producing cells in peritoneal
lavage fluid revealed increased numbers of IL-5-producing cells in both
T cell and NK cell populations following allergen exposure. Depletion
of NK cells by treatment with NK1.1 Abs selectively reduced the number
of infiltrating eosinophils by more than 50%. Moreover, the inhibition
of the infiltration of eosinophils was accompanied by a complete loss
of IL-5-producing NK cells and significantly reduced levels of
peritoneal lavage fluid IL-5, whereas the number of IL-5-producing T
cells was not affected. Thus, the results presented in this study
provide clear evidence for a novel immunoregulatory function of NK
cells in vivo, promoting allergen-induced eosinophilic inflammatory
responses by the production of IL-5.
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