Distinction between IL‐13+ and IFN‐γ+ natural killer cells and regulation of their pool size by IL‐4

The hypothesis that distinct subsets of NK cells produce type 2 and type 1 cytokines in resting naive lymphocytes was tested analyzing cytokine production at the single‐cell level. Two non‐overlapping IL‐13+ and IFN‐γ+ subsets were identified in adult and neonatal NK cells. IL‐2 maintained their relative proportion. Accumulation of the former was induced by IL‐4, but not IL‐13, and inhibited by IL‐12; that of the latter was induced by IL‐12 and inhibited by IL‐4 and IL‐13. IL‐4 induced preferential proliferation of the pre‐existing peripheral IL‐13+ cells, whereas IL‐12 had minimal effect on proliferation of the IFN‐γ+ NK cells. The IL‐13+ cells (CD161+ only) are phenotypically distinct from the IFN‐γ+ones (CD56+) before and after culture under any condition analyzed, and produce IL‐13 in response to NK‐sensitive target cells and PMA + Ca2+ ionophore, whereas also FcγRIIIA and IL‐2 + IL‐12 stimulate IFN‐γ production. These data define the existence and regulation of two distinct resting peripheral NK cell subsets producing type 1 and type 2 cytokines, and suggest possible roles for IL‐13+ NK cells in allergy.

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