title: The biology of NK cells and their receptors affects clinical outcomes after hematopoietic cell transplantation (HCT).
abstract: Natural killer (NK) cells were first identified for their capacity to reject bone marrow allografts in lethally irradiated mice without prior sensitization. Subsequently, human NK cells were detected and defined by their non-major histocompatibility complex (MHC)-restricted cytotoxicity toward transformed or virally infected target cells. Karre et al. later proposed 'the missing self hypothesis' to explain the mechanism by which self-tolerant cells could kill targets that had lost self MHC class I. Subsequently, the receptors that recognize MHC class I to mediate tolerance in the host were identified on NK cells. These class I-recognizing receptors contribute to the acquisition of function by a dynamic process known as NK cell education or licensing. In the past, NK cells were assumed to be short lived, but more recently NK cells have been shown to mediate immunologic memory to secondary exposures to cytomegalovirus infection. Because of their ability to lyse tumors with aberrant MHC class I expression and to produce cytokines and chemokines upon activation, NK cells may be primed by many stimuli, including viruses and inflammation, to contribute to a graft-versus-tumor effect. In addition, interactions with other immune cells support the therapeutic potential of NK cells to eradicate tumor and to enhance outcomes after hematopoietic cell transplantation.
authors: Adult, Oncology and Transplantation, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA.
authors: Bree
authors: B
authors: Foley
authors: Adult, Oncology and Transplantation, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA.
authors: Martin
authors: M
authors: Felices
authors: Adult, Oncology and Transplantation, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA.
authors: Frank
authors: F
authors: Cichocki
authors: Adult, Oncology and Transplantation, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA.
authors: Sarah
authors: S
authors: Cooley
authors: Pediatric Hematology, Oncology and Transplantation, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA.
authors: Michael R
authors: MR
authors: Verneris
authors: Adult, Oncology and Transplantation, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA.
authors: Jeffrey S
authors: JS
authors: Miller
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D055607:Receptors, Natural Killer Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D055607:Receptors, Natural Killer Cell
keywords: NK cells; cytomegalovirus; innate immunity; killer immunoglobulin-like receptors; leukemia; transplantation