title: Oxidative stress mediates a reduced expression of the activating receptor NKG2D in NK cells from end-stage renal disease patients.
abstract: To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed NK cell subset analysis in 66 patients with ESRD treated by hemodialysis (n = 59) or peritoneal dialysis (n = 7). Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D(+) cells within both the CD8(+) T cell (58% vs 67%, p = 0.03) and NK cell (39% vs 56%, p = 0.002) populations. CD56(dim) cells, which comprise the majority of NK cells in the periphery, were more affected in this regard than were CD56(bright) cells. Uremic serum could decrease NKG2D expression on NK cells from healthy donors. Among factors that could contribute to the decrease in NKG2D expression in ESRD patients, reactive oxygen species (ROS) play a major role. We found that catalase could reverse the effects of uremic serum on NKG2D expression (p < 0.001) and that ROS down-regulated NKG2D at the mRNA level and at the NK cell surface. Additionally, ESRD patients had both increased membrane-bound MHC class I-related chain A (MICA) on monocytes (p = 0.04) and increased soluble MICA (203 pg/ml vs 110 pg/ml; p < 0.001). Both ROS and uremic serum could significantly increase in vitro the expression of the NKG2D ligand MICA on the renal epithelial cell line HK-2. Taken together, these studies suggest for the first time that both low NKG2D expression and up-regulation of its ligand MICA are related to ROS production and may be involved in the immune deficiency of ESRD patients.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U662, Paris, France. marie-noelle.peraldi@sls.aphp.fr
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Peraldi
authors.forename: Jeannig
authors.initials: J
authors.lastname: Berrou
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dulphy
authors.forename: Alexandre
authors.initials: A
authors.lastname: Seidowsky
authors.forename: Philippe
authors.initials: P
authors.lastname: Haas
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boissel
authors.forename: Fabien
authors.initials: F
authors.lastname: Metivier
authors.forename: Christine
authors.initials: C
authors.lastname: Randoux
authors.forename: Niloufar
authors.initials: N
authors.lastname: Kossari
authors.forename: Alain
authors.initials: A
authors.lastname: Guérin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Geffroy
authors.forename: Guy
authors.initials: G
authors.lastname: Delavaud
authors.forename: Viviana
authors.initials: V
authors.lastname: Marin-Esteban
authors.forename: Denis
authors.initials: D
authors.lastname: Glotz
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008231:Lymphopenia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D018384:Oxidative Stress / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000097:blood; D015854:Up-Regulation / Q000276:immunology; D014511:Uremia / Q000097:blood
chemical_list: D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D017382:Reactive Oxygen Species