title: NK Cell Functional Impairment after Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with Reduced Levels of T-bet and Eomesodermin.
abstract: NK cells play a major role in protection against tumor recurrence and infection after allogeneic hematopoietic stem cell transplantation (HSCT). It has been shown that NK cell function after HSCT is impaired, but underlying molecular mechanisms are not well-known. In this report we show that the level of T-bet and Eomesodermin (Eomes), two T-box transcription factors regulating lymphocyte effector functions, is strongly reduced in NK cells from HSCT recipients compared with healthy control subjects. Reduction of T-bet and Eomes expression appeared early and persisted for years after HSCT, affecting all peripheral blood NK cells independently of their differentiation status. Reduced T-bet levels in NK cells from allogeneic HSCT recipients significantly correlated with reduced perforin expression. Acute, but not chronic, graft-versus-host disease, as well as CMV reactivation, was associated with further downregulation of T-bet expression in NK cells. Lower levels of T-bet expression in NK cells were associated with less favorable outcome after HSCT as a result of increased nonrelapse mortality. Collectively, our results provide a possible molecular explanation for the previously reported functional exhaustion of NK cells after allogeneic HSCT and suggest an impact of the NK transcriptional machinery status on HSCT outcome.
authors.affiliation: Division of Hematology, Department of Medical Specialties, Geneva University Hospitals, University of Geneva, CH-1211 Geneva 14, Switzerland federico.simonetta@hcuge.ch.
authors.forename: Federico
authors.initials: F
authors.lastname: Simonetta
authors.affiliation: Division of Hematology, Department of Medical Specialties, Geneva University Hospitals, University of Geneva, CH-1211 Geneva 14, Switzerland.
authors.forename: Amandine
authors.initials: A
authors.lastname: Pradier
authors.affiliation: Division of Hematology, Department of Medical Specialties, Geneva University Hospitals, University of Geneva, CH-1211 Geneva 14, Switzerland.
authors.forename: Carine
authors.initials: C
authors.lastname: Bosshard
authors.affiliation: Division of Hematology, Department of Medical Specialties, Geneva University Hospitals, University of Geneva, CH-1211 Geneva 14, Switzerland.
authors.forename: Stavroula
authors.initials: S
authors.lastname: Masouridi-Levrat
authors.affiliation: Division of Hematology, Department of Medical Specialties, Geneva University Hospitals, University of Geneva, CH-1211 Geneva 14, Switzerland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Chalandon
authors.affiliation: Division of Hematology, Department of Medical Specialties, Geneva University Hospitals, University of Geneva, CH-1211 Geneva 14, Switzerland.
authors.forename: Eddy
authors.initials: E
authors.lastname: Roosnek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019002:CD56 Antigen / Q000096:biosynthesis; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000096:biosynthesis; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D055815:Young Adult; D000098815:T-bet Transcription Factor
chemical_list: D019002:CD56 Antigen; C491199:EOMES protein, human; C522918:NCAM1 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D054353:Perforin