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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-γ, 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.

This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.

SummaryBackground and objectives Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, receptor activator of NF-kB ligand, inflammatory markers, and progression of coronary artery calcification score.Design, setting, participants, & measurements Seventy-eight hemodialysis patients were enrolled. Serum IL-1b, IL-6, TNF-a, osteoprotegerin, receptor activator of NF-kB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive.Results Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.3969.67 versus 12.9066.59 pmol/L, P=0.02; 35.17618.35 versus 24611.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-kB ligand at 1 year was significantly higher in the progressive group (0.26 [0.15-0.46] versus 0.18 [0.12-0.28], P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-kB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=20.29, P=0.01) and 1 year (r=20.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model. ConclusionsBaseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.

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