title: The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease.
abstract: Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E). Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD). Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention.
authors: Department of Bone Marrow Transplantation, University Hospital Essen, Essen 45147, Germany. lambros.kordelas@uk-essen.de.
authors: Lambros
authors: L
authors: Kordelas
authors: Department of Bone Marrow Transplantation, University Hospital Essen, Essen 45147, Germany. Nina-Kristin.Steckel@uk-essen.de.
authors: Nina-Kristin
authors: NK
authors: Steckel
authors: Institute for Transfusion Medicine, University Hospital Essen, Essen 45147, Germany. Peter.Horn@uk-essen.de.
authors: Peter A
authors: PA
authors: Horn
authors: Department of Bone Marrow Transplantation, University Hospital Essen, Essen 45147, Germany. Dietrich.Beelen@uk-essen.de.
authors: Dietrich W
authors: DW
authors: Beelen
authors: Institute for Transfusion Medicine, University Hospital Essen, Essen 45147, Germany. vera.rebmann@uk-essen.de.
authors: Vera
authors: V
authors: Rebmann
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000096:biosynthesis* / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000096:biosynthesis* / Q000276:immunology; D033581:Stem Cell Transplantation / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000009:adverse effects; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D000097625:HLA-E Antigens; C497869:KLRD1 protein, human
keywords: NK cells; NKG2C receptor; allogeneic stem cell transplantation; graft-versus-host disease