Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56 bright NKG2A +++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content.

Autor: Dobbs K; Laboratory of Host Defenses, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Tabellini G; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Calzoni E; 'A. Nocivelli Institute for Molecular Medicine', Pediatric Clinic, University of Brescia, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Italy., Patrizi O; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Martinez P; Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina., Giliani SC; 'A. Nocivelli Institute for Molecular Medicine', Pediatric Clinic, University of Brescia, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Italy., Moratto D; 'A. Nocivelli Institute for Molecular Medicine', Pediatric Clinic, University of Brescia, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Italy., Al-Herz W; Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait., Cancrini C; DPUO, Division of Immuno-Infectivology, University Department of Pediatrics, Bambino Gesù Children's Hospital, Rome, Italy.; School of Medicine, University of Tor Vergata, Rome, Italy., Cowan M; Pediatric Allergy Immunology and Blood and Marrow Transplant Division, University of California San Francisco, Benioff Children's Hospital, San Francisco, CA, United States., Bleesing J; Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Booth C; Institute for Immunity and Transplantation, University College London, London, United Kingdom., Buchbinder D; Division of Pediatric Hematology, Children's Hospital Orange County, University of California Irvine, Orange County, CA, United States., Burns SO; Institute for Immunity and Transplantation, University College London, London, United Kingdom.; Department of Immunology, Royal Free London NHS Foundation Trust, London, United Kingdom., Chatila TA; Division of Immunology, Boston Children's Hospital, Boston, MA, United States., Chou J; Division of Immunology, Boston Children's Hospital, Boston, MA, United States., Daza-Cajigal V; Institute for Immunity and Transplantation, University College London, London, United Kingdom., Ott de Bruin LM; Division of Immunology, Boston Children's Hospital, Boston, MA, United States., de la Morena M; Division of Allergy and Immunology, Southwestern Medical Center, University of Texas, Dallas, TX, United States., Di Matteo G; DPUO, Division of Immuno-Infectivology, University Department of Pediatrics, Bambino Gesù Children's Hospital, Rome, Italy.; School of Medicine, University of Tor Vergata, Rome, Italy., Finocchi A; DPUO, Division of Immuno-Infectivology, University Department of Pediatrics, Bambino Gesù Children's Hospital, Rome, Italy.; School of Medicine, University of Tor Vergata, Rome, Italy., Geha R; Division of Immunology, Boston Children's Hospital, Boston, MA, United States., Goyal RK; Division of Hematology/Oncology/BMT, Children's Mercy Hospital & Clinics, Kansas City, MO, United States., Hayward A; Department of Pediatrics, Brown University, Providence, RI, United States., Holland S; Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Huang CH; Department of Paediatrics, National University Hospital, Singapore, Singapore., Kanariou MG; Department of Immunology-Histocompatibility, 'Aghia Sophia' Children's Hospital, Athens, Greece., King A; Division of Pediatric Immunology, Hospital Luis Calvo Mackenna, Santiago, Chile., Kaplan B; Department of Pediatrics, Division of Allergy and Immunology, Hofstra Northwell School of Medicine, Hofstra University, Great Neck, NY, United States., Kleva A; Department of Pediatrics, Division of Allergy and Immunology, Hofstra Northwell School of Medicine, Hofstra University, Great Neck, NY, United States., Kuijpers TW; Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands., Lee BW; Department of Paediatrics, National University Hospital, Singapore, Singapore., Lougaris V; Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy., Massaad M; Division of Immunology, Boston Children's Hospital, Boston, MA, United States., Meyts I; Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium., Morsheimer M; Transplantation Branch, Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States., Neven B; Pediatric Hematology-Immunology Department, Hospital Necker-Enfants Malades, Institut Imagine, AP-HP, Paris Descartes University, Sorbonne-Paris-Cité, Paris, France., Pai SY; Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA, United States., Parvaneh N, Plebani A; Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy., Prockop S; Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, United States., Reisli I; Division of Pediatric Immunology and Allergy, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey., Soh JY; Department of Paediatrics, National University Hospital, Singapore, Singapore., Somech R; Pediatric Immunology Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Torgerson TR; Department of Pediatrics and Immunology, Seattle Children's Hospital, University of Washingtin, Seattle, WA, United States., Kim YJ; Division of Infectious Diseases and Immunodeficiency, Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea., Walter JE; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States., Gennery AR; Department of Paediatric Immunology, Great North Children's Hospital, Newcastle Upon Tyne, United Kingdom.; Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom., Keles S; Division of Pediatric Immunology and Allergy, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey., Manis JP; Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, United States., Marcenaro E; Molecular Immunology Laboratories, Department of Experimental Medicine, University of Genoa, Genoa, Italy., Moretta A; Molecular Immunology Laboratories, Department of Experimental Medicine, University of Genoa, Genoa, Italy., Parolini S; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Notarangelo LD; Laboratory of Host Defenses, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2017 Jul 17; Vol. 8, pp. 798. Date of Electronic Publication: 2017 Jul 17 (Print Publication: 2017).
DOI: 10.3389/fimmu.2017.00798
Abstrakt: Mutations of the recombinase-activating genes 1 and 2 ( RAG1 and RAG2 ) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment; however, high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that Rag -/- natural killer (NK) cells have a mature phenotype, reduced fitness, and increased cytotoxicity. We aimed to analyze NK cell phenotype and function in patients with mutations in RAG and in non-homologous end joining (NHEJ) genes. Here, we provide evidence that NK cells from these patients have an immature phenotype, with significant expansion of CD56 bright CD16 -/int CD57 - cells, yet increased degranulation and high perforin content. Correlation was observed between in vitro recombinase activity of the mutant proteins, NK cell abnormalities, and in vivo clinical phenotype. Addition of serotherapy in the conditioning regimen, with the aim of depleting the autologous NK cell compartment, may be important to facilitate engraftment and immune reconstitution in patients with RAG and NHEJ defects treated by HSCT.
Databáze: MEDLINE