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 (P = 0·028) NK cells and more CD56 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 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 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.