Increased NK 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, NKT 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)-R+, IL-4(+), transforming growth factor (TGF)-(+), IL-4(+) human leucocyte antigen D-related (HLA-DR)(+), TGF-(+)HLA-DR+, IL-4(+)TGF-(+), IL-4(+)TGF-(-), IFN-(+) and/or IL-10(-)IFN-(+) (all P001), more IL-17(+)CD56(bright) (P=0028) NK cells and more CD56(dim)CD16(+) NK cells co-expressing IFN-R, IFN-, IL-4 and/or TGF- (all P001). 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<005), NKG2D(+)NKG2A(+), NKG2D (+)NKG2A(-), NKG2D(+) and/or NKG2A(+) (all P001) CD56(+) NK cells and higher CD158a(+), CD158b(+) (all P<005), NKG2D(+) and/or NKG2A(+) (all P<001) 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<005) 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.