Broad Impairment of Natural Killer Cells From Operationally Tolerant Kidney Transplanted Patients
The role of natural killer (NK) cells in organ transplantation is controversial. This study aims to decipher their role in kidney transplant tolerance in humans. Previous studies highlighted several modulated genes involved in NK cell biology in blood from spontaneously operationally tolerant patien...
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Frontiers Media S.A.
2017-12-01
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Series: | Frontiers in Immunology |
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Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01721/full |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Emilie Dugast Emilie Dugast Gaëlle David Gaëlle David Romain Oger Richard Danger Richard Danger Jean-Paul Judor Jean-Paul Judor Katia Gagne Katia Gagne Katia Gagne Mélanie Chesneau Mélanie Chesneau Nicolas Degauque Nicolas Degauque Jean-Paul Soulillou Jean-Paul Soulillou Pascale Paul Christophe Picard Christophe Picard Pierrick Guerif Pierrick Guerif Pierrick Guerif Sophie Conchon Sophie Conchon Magali Giral Magali Giral Magali Giral Nadine Gervois Christelle Retière Christelle Retière Sophie Brouard Sophie Brouard |
spellingShingle |
Emilie Dugast Emilie Dugast Gaëlle David Gaëlle David Romain Oger Richard Danger Richard Danger Jean-Paul Judor Jean-Paul Judor Katia Gagne Katia Gagne Katia Gagne Mélanie Chesneau Mélanie Chesneau Nicolas Degauque Nicolas Degauque Jean-Paul Soulillou Jean-Paul Soulillou Pascale Paul Christophe Picard Christophe Picard Pierrick Guerif Pierrick Guerif Pierrick Guerif Sophie Conchon Sophie Conchon Magali Giral Magali Giral Magali Giral Nadine Gervois Christelle Retière Christelle Retière Sophie Brouard Sophie Brouard Broad Impairment of Natural Killer Cells From Operationally Tolerant Kidney Transplanted Patients Frontiers in Immunology natural killer cytotoxicity tolerance kidney transplantation |
author_facet |
Emilie Dugast Emilie Dugast Gaëlle David Gaëlle David Romain Oger Richard Danger Richard Danger Jean-Paul Judor Jean-Paul Judor Katia Gagne Katia Gagne Katia Gagne Mélanie Chesneau Mélanie Chesneau Nicolas Degauque Nicolas Degauque Jean-Paul Soulillou Jean-Paul Soulillou Pascale Paul Christophe Picard Christophe Picard Pierrick Guerif Pierrick Guerif Pierrick Guerif Sophie Conchon Sophie Conchon Magali Giral Magali Giral Magali Giral Nadine Gervois Christelle Retière Christelle Retière Sophie Brouard Sophie Brouard |
author_sort |
Emilie Dugast |
title |
Broad Impairment of Natural Killer Cells From Operationally Tolerant Kidney Transplanted Patients |
title_short |
Broad Impairment of Natural Killer Cells From Operationally Tolerant Kidney Transplanted Patients |
title_full |
Broad Impairment of Natural Killer Cells From Operationally Tolerant Kidney Transplanted Patients |
title_fullStr |
Broad Impairment of Natural Killer Cells From Operationally Tolerant Kidney Transplanted Patients |
title_full_unstemmed |
Broad Impairment of Natural Killer Cells From Operationally Tolerant Kidney Transplanted Patients |
title_sort |
broad impairment of natural killer cells from operationally tolerant kidney transplanted patients |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-12-01 |
description |
The role of natural killer (NK) cells in organ transplantation is controversial. This study aims to decipher their role in kidney transplant tolerance in humans. Previous studies highlighted several modulated genes involved in NK cell biology in blood from spontaneously operationally tolerant patients (TOLs; drug-free kidney-transplanted recipients with stable graft function). We performed a phenotypic, functional, and genetic characterization of NK cells from these patients compared to kidney-transplanted patients with stable graft function under immunosuppression and healthy volunteers (HVs). Both operationally TOLs and stable patients harbored defective expression of the NKp46 activator receptor and lytic molecules perforin and granzyme compared to HVs. Surprisingly, NK cells from operationally TOLs also displayed decreased expression of the CD16 activating marker (in the CD56Dim NK cell subset). This decrease was associated with impairment of their functional capacities upon stimulation, as shown by lower interferon gamma (IFNγ) production and CD107a membranous expression in a reverse antibody-dependent cellular cytotoxicity (ADCC) assay, spontaneous lysis assays, and lower target cell lysis in the 51Cr release assay compared to HVs. Conversely, despite impaired K562 cell lysis in the 51Cr release assay, patients with stable graft function harbored a normal reverse ADCC and even increased amounts of IFNγ+ NK cells in the spontaneous lysis assay. Altogether, the strong impairment of the phenotype and functional cytotoxic capacities of NK cells in operationally TOLs may accord with the establishment of a pro-tolerogenic environment, despite remaining highly activated after transplantation in patients with stable graft function. |
topic |
natural killer cytotoxicity tolerance kidney transplantation |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01721/full |
work_keys_str_mv |
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doaj-d9c8d9fa0f8042abb15d408f7485a62a2020-11-25T00:50:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-12-01810.3389/fimmu.2017.01721312035Broad Impairment of Natural Killer Cells From Operationally Tolerant Kidney Transplanted PatientsEmilie Dugast0Emilie Dugast1Gaëlle David2Gaëlle David3Romain Oger4Richard Danger5Richard Danger6Jean-Paul Judor7Jean-Paul Judor8Katia Gagne9Katia Gagne10Katia Gagne11Mélanie Chesneau12Mélanie Chesneau13Nicolas Degauque14Nicolas Degauque15Jean-Paul Soulillou16Jean-Paul Soulillou17Pascale Paul18Christophe Picard19Christophe Picard20Pierrick Guerif21Pierrick Guerif22Pierrick Guerif23Sophie Conchon24Sophie Conchon25Magali Giral26Magali Giral27Magali Giral28Nadine Gervois29Christelle Retière30Christelle Retière31Sophie Brouard32Sophie Brouard33Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceEtablissement Français du sang, Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, Nantes, FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceEtablissement Français du sang, Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, Nantes, FranceLabEx Transplantex, Université de Strasbourg, FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceNephrology Dialysis Renal Transplantation Center, Assistance Publique des Hôpitaux de Marseille, Hospital de la Conception, UMR 1076, Vascular Research Center of Marseille, INSERM, Aix-Marseille University, Marseille, FranceÉtablissement Français du Sang Alpes Méditerranée, Marseille, FranceADES UMR 7268, CNRS, EFS, Aix-Marseille Université, Marseille, FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceCIC Biotherapy, CHU Nantes, Nantes, FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceCIC Biotherapy, CHU Nantes, Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, Nantes, FranceEtablissement Français du sang, Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, Nantes, FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, FranceInstitut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceThe role of natural killer (NK) cells in organ transplantation is controversial. This study aims to decipher their role in kidney transplant tolerance in humans. Previous studies highlighted several modulated genes involved in NK cell biology in blood from spontaneously operationally tolerant patients (TOLs; drug-free kidney-transplanted recipients with stable graft function). We performed a phenotypic, functional, and genetic characterization of NK cells from these patients compared to kidney-transplanted patients with stable graft function under immunosuppression and healthy volunteers (HVs). Both operationally TOLs and stable patients harbored defective expression of the NKp46 activator receptor and lytic molecules perforin and granzyme compared to HVs. Surprisingly, NK cells from operationally TOLs also displayed decreased expression of the CD16 activating marker (in the CD56Dim NK cell subset). This decrease was associated with impairment of their functional capacities upon stimulation, as shown by lower interferon gamma (IFNγ) production and CD107a membranous expression in a reverse antibody-dependent cellular cytotoxicity (ADCC) assay, spontaneous lysis assays, and lower target cell lysis in the 51Cr release assay compared to HVs. Conversely, despite impaired K562 cell lysis in the 51Cr release assay, patients with stable graft function harbored a normal reverse ADCC and even increased amounts of IFNγ+ NK cells in the spontaneous lysis assay. Altogether, the strong impairment of the phenotype and functional cytotoxic capacities of NK cells in operationally TOLs may accord with the establishment of a pro-tolerogenic environment, despite remaining highly activated after transplantation in patients with stable graft function.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01721/fullnatural killercytotoxicitytolerancekidneytransplantation |