Increased natural killer cell subsets with inhibitory cytokines and inhibitory surface receptors in patients with recurrent miscarriage and decreased or normal subsets in kidney transplant recipients late post-transplant.

Patients with recurrent miscarriage (RM) show up-regulated cytotoxic natural killer (NK) cells that are suspected to play a causal role in abortion. In the present study, we investigated counter-regulating inhibitory mechanisms and compared the results in RM patients with those of healthy controls (HC), patients with end-stage renal disease (ESRD) and kidney transplant recipients late post-transplant (TX). NK, NK T and T cell subsets were analysed in the peripheral blood of 31 RM, 14 female ESRD and nine female TX patients as well as 21 female HC using eight-colour fluorescence flow cytometry. Compared with HC, RM patients showed significantly higher absolute numbers of CD56(+) NK cells co-expressing the phenotype interferon (IFN)-γR(+) , IL-4(+) , transforming growth factor (TGF)-β(+) , IL-4(+) human leucocyte antigen D-related (HLA-DR)(+) , TGF-β(+) HLA-DR(+) , IL-4(+) TGF-β(+) , IL-4(+) TGF-β(-) , IFN-γ(+) and/or IL-10(-) IFN-γ(+) (all P ≤ 0·01), more IL-17(+) CD56(bright) (P = 0·028) NK cells and more CD56(dim) CD16(+) NK cells co-expressing IFN-γR, IFN-γ, IL-4 and/or TGF-β (all P ≤ 0·01). When the same cell subsets were analysed in ESRD or TX patients, cytokine-producing NK cell subsets were not significantly different from those of HC. RM patients showed significantly higher absolute numbers of CD158a(+) , CD158b(+) , CD158a(-) CD158e(+) (all P < 0·05), NKG2D(+) NKG2A(+) , NKG2D (+) NKG2A(-) , NKG2D(+) and/or NKG2A(+) (all P ≤ 0·01) CD56(+) NK cells and higher CD158a(+) , CD158b(+) (all P < 0·05), NKG2D(+) and/or NKG2A(+) (all P < 0·01) CD56(dim+) CD16(+) NK cells than HC. In contrast, ESRD patients had normal and TX recipients had lower CD158a(+) and NKG2D(+) NKG2A(-) CD56(+) NK cells and lower CD158a(+) CD56(dim+) CD16(+) NK cells (all P < 0·05) than HC. RM patients have abnormally high circulating NK cells expressing inhibitory cytokines and inhibitory surface receptors which might contribute to the pathogenesis of RM.