Li Zhu1, Mostafa Aly2, Haihao Wang3, Hristos Karakizlis4, Rolf Weimer4, Christian Morath5, Ruben Jeremias Kuon6, Bettina Toth7, Naruemol Ekpoom8, Gerhard Opelz8, Volker Daniel9. 1. Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany; Department of Hematology, Tongji Hospital, Huazhong University of Science and Technology, 430030 Wuhan, China. 2. Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany; Nephrology Unit, Internal Medicine Department, Assiut University, Egypt. 3. Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, 430030 Wuhan, China. 4. Department of Internal Medicine, University of Giessen, Klinikstrasse 33, D-35385 Giessen, Germany. 5. Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany. 6. Department of Obstetrics and Gynecology, University Hospital Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany. 7. Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. 8. Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. 9. Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Electronic address: volker.daniel@med.uni-heidelberg.de.
Abstract
BACKGROUND: There is evidence that NK cells with low cytotoxicity but strong immunoregulatory characteristics contribute to good graft outcome. We attempted to investigate which NK cell subsets increase post-transplant and might affect graft function. METHOD: Lymphocyte and NK cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients pre-transplant and post-transplant. In total, 31 transplant recipients were studied. RESULTS: When cell numbers were compared in 9 patients pre- and 6 months post-transplant, post-transplant CD56dimCD16+ (p = 0.011) NK cells with the phenotype CD158a+ (p = 0.008), CD158e+ (p = 0.038), NKG2A+ (p = 0.008), NKG2D+ (p = 0.011), IFNyR+ (p = 0.008), perforin+ (p = 0.008), granzymeB+ (p = 0.008), perforin+granzymeB+ (p = 0.008) and perforin-granzymeB- (p = 0.021) were lower than those pre-transplant, indicating a post-transplant reduction of cytotoxic NK cells. In 28 patients NK cell subsets were analyzed with respect to time post-transplant (median 888 days post-transplant). CD56dimCD16+ NK cells co-expressing CD158a (p = 0.014), NKG2D (p = 0.047), IL4R (p = 0.038), IL10R (p = 0.008) and IFNy (p = 0.036) as well as CD56bright NK cells with the phenotype TGFß+ (p = 0.017), TGFR+ (p = 0.035), CD158a+ (p = 0.042) and perforin-granzymeB- (p = 0.048) increased with time post-transplant. CONCLUSION: Post-transplant, cytotoxic NK cells were lower than pre-transplant and remained low, whereas NK cell subsets with potentially immunoregulatory properties increased.
BACKGROUND: There is evidence that NK cells with low cytotoxicity but strong immunoregulatory characteristics contribute to good graft outcome. We attempted to investigate which NK cell subsets increase post-transplant and might affect graft function. METHOD: Lymphocyte and NK cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients pre-transplant and post-transplant. In total, 31 transplant recipients were studied. RESULTS: When cell numbers were compared in 9 patients pre- and 6 months post-transplant, post-transplant CD56dimCD16+ (p = 0.011) NK cells with the phenotype CD158a+ (p = 0.008), CD158e+ (p = 0.038), NKG2A+ (p = 0.008), NKG2D+ (p = 0.011), IFNyR+ (p = 0.008), perforin+ (p = 0.008), granzymeB+ (p = 0.008), perforin+granzymeB+ (p = 0.008) and perforin-granzymeB- (p = 0.021) were lower than those pre-transplant, indicating a post-transplant reduction of cytotoxic NK cells. In 28 patients NK cell subsets were analyzed with respect to time post-transplant (median 888 days post-transplant). CD56dimCD16+ NK cells co-expressing CD158a (p = 0.014), NKG2D (p = 0.047), IL4R (p = 0.038), IL10R (p = 0.008) and IFNy (p = 0.036) as well as CD56bright NK cells with the phenotype TGFß+ (p = 0.017), TGFR+ (p = 0.035), CD158a+ (p = 0.042) and perforin-granzymeB- (p = 0.048) increased with time post-transplant. CONCLUSION: Post-transplant, cytotoxic NK cells were lower than pre-transplant and remained low, whereas NK cell subsets with potentially immunoregulatory properties increased.
Authors: Li Zhu; Hristos Karakizlis; Rolf Weimer; Christian Morath; Naruemol Ekpoom; Eman H Ibrahim; Gerhard Opelz; Volker Daniel Journal: Ann Transplant Date: 2020-12-22 Impact factor: 1.530