title: Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence.
abstract: OBJECTIVE
  The Nijmegen breakage syndrome (NBS) is an inherited genetic disorder characterized by a typical facial appearance, microcephaly, growth retardation, immunodeficiency, and a strong predisposition to malignancies, especially of lymphoid origin. NBS patients have a mutation in the NBN gene which involves the repair of DNA double-strand breaks (DSBs). Here we studied the peripheral T cell compartment of NBS patients with a focus on immunological senescence.
  
  
  METHODS
  The absolute numbers and frequencies of the different T cell subsets were determined in NBS patients from young age till adulthood and compared to age-matched healthy individuals (HI). In addition, we determined the expression of senescent T cell markers and the signal joint T cell receptor excision circles (sjTRECs) content.
  
  
  RESULTS
  Our results demonstrate that NBS patients have reduced T cell numbers. NBS patients showed lower numbers of αβ+T cells, but normal γδ+T cell numbers compared to HI. Concerning the αβ+T cells, both CD4+as well as CD8+T cells were excessively reduced in numbers compared to aged-matched HI. In addition, NBS patients showed higher frequencies of the more differentiated T cells expressing the senescent cell marker CD57 and did not express co-stimulatory molecule CD28. These effects were already present in the youngest age group. Furthermore, NBS patients showed lower sjTREC content in their T cells possibly indicative of a lower thymic output.
  
  
  CONCLUSIONS
  We conclude that circulating T cells from NBS patients show signs of a senescent phenotype which is already present from young age on and which might explain their T cell immune deficiency.
authors.affiliation: Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. r.meijers@erasmusmc.nl.
authors.forename: Ruud W J
authors.initials: RWJ
authors.lastname: Meijers
authors.affiliation: Department of Clinical Microbiology and Immunology, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dzierzanowska-Fangrat
authors.affiliation: Department of Clinical Microbiology and Immunology, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zborowska
authors.affiliation: Department of Clinical Microbiology and Immunology, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Solarska
authors.affiliation: Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Tielemans
authors.affiliation: Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Bob A C
authors.initials: BAC
authors.lastname: van Turnhout
authors.affiliation: Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Gertjan
authors.initials: G
authors.lastname: Driessen
authors.affiliation: Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
authors.affiliation: Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Jacques J M
authors.initials: JJM
authors.lastname: van Dongen
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Krystyna H
authors.initials: KH
authors.lastname: Chrzanowska
authors.affiliation: Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
mesh_terms: D000293:Adolescent; D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D016922:Cellular Senescence / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D018655:Lymphocyte Count; D008297:Male; D009154:Mutation; D049932:Nijmegen Breakage Syndrome / Q000097:blood* / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: CD28null; NBS; T cells; senescence; sjTREC