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

• Published in: Clinical and experimental immunology 2018-08, Vol.193 (2), p.241-254
• Main Authors: Zhu, L., Aly, M., Wang, H., Karakizlis, H., Weimer, R., Morath, C., Kuon, R. J., Toth, B., Ekpoom, N., Opelz, G., Daniel, V.
• Format: Article
• Language: English
• Subjects: Abortion, Habitual - immunology; Adult; Aged; CD16 antigen; CD56 antigen; Cytokines; Cytokines - metabolism; Cytotoxicity; Female; Flow Cytometry; Fluorescence; Graft Rejection - immunology; Histocompatibility antigen HLA; Humans; Immunophenotyping; inhibitory cytokines; inhibitory surface receptors; Interferon; kidney transplant recipients late post‐transplant; Kidney Transplantation; Kidney transplants; Killer Cells, Natural - immunology; Lymphocyte receptors; Lymphocyte Subsets - immunology; Lymphocytes; Lymphocytes T; Middle Aged; Miscarriage; Natural killer cells; NK cell subsets; NKG2 antigen; Original; patients with recurrent miscarriage; Peripheral blood; Phenotypes; Pregnancy; Receptors, Natural Killer Cell - metabolism; Transforming growth factor; Transplant Recipients; Young Adult
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13142

Summary 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+CD56bright (P = 0·028) NK cells and more CD56dimCD16+ 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