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* Institute of Experimental Medicine, Department of Immunology, Istanbul University, Istanbul, Turkey;
Akdeniz University Medical Faculty, Department of Pediatrics, Antalya, Turkey; and
Swiss Institute of Allergy and Asthma Research, Davos, Switzerland
The immune system has a variety of regulatory/suppressive processes, which are decisive for the development of a healthy or an allergic immune response to allergens. NK1 and NK2 subsets have been demonstrated to display counterregulatory and provocative roles in immune responses, similar to Th1 and Th2 cells. T regulatory cells suppressing both Th1 and Th2 responses have been the focus of intensive research during the last decade. In this study, we aimed to investigate regulatory NK cells in humans, by characterization of NK cell subsets according to their IL-10 secretion property. Freshly purified IL-10-secreting NK cells expressed up to 40-fold increase in IL-10, but not in the FoxP3 and TGF-β mRNAs. PHA and IL-2 stimulation as well as vitamin D3/dexamethasone and anti-CD2/CD16 mAbs are demonstrated to induce IL-10 expression in NK cells. The effect of IL-10+ NK cells on Ag-specific T cell proliferation has been examined in bee venom major allergen, phospholipase A2- and purified protein derivative of Mycobecterium bovis-induced T cell proliferation. IL-10+ NK cells significantly suppressed both allergen/Ag-induced T cell proliferation and secretion of IL-13 and IFN-
, particularly due to secreted IL-10 as demonstrated by blocking of the IL-10 receptor. These results demonstrate that a distinct small fraction of NK cells display regulatory functions in humans.
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1 This work was supported by the Swiss National Science Foundation (Grants SNF-32-112306/1, 32-118226), and Global Allergy and Asthma European Network (GA2LEN).
2 Address correspondence and reprint requests to Dr. Gunnur Deniz, Istanbul University, Institute of Experimental Medicine, Department of Immunology, Vakif Gureba Caddesi 34280, Sehremini, Istanbul, Turkey. E-mail address: gdeniz{at}istanbul.edu.tr
3 Abbreviations used in this paper: KIR, killer cell Ig-like receptor; TReg, T regulatory cell; PLA, phospholipase A2; PPD, purified protein derivative.
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