Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia

AR Exley, S Buckenham, E Hodges, R Hallam, Philip Byrd, James Last, C Trinder, S Harris, N Screaton, AP Williams, Alexander Taylor, JM Shneerson

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

ATM kinase modulates pathways implicated in premature ageing and ATM genotype predicts survival, yet immunodeficiency in ataxia telangiectasia is regarded as mild and unrelated to age. We address this paradox in a molecularly characterised sequential adult cohort with classical and mild variant ataxia telangiectasia. Immunodeficiency has the characteristics of premature ageing across multiple cellular and molecular immune parameters. This immune ageing occurs without previous CMV infection. Age predicts immunodeficiency in genetically homogeneous ataxia telangiectasia, and in comparison with controls, calendar age is exceeded by immunological age defined by thymic naive CD4+ T cell levels. Applying ataxia telangiectasia as a model of immune ageing, pneumococcal vaccine responses, characteristically deficient in physiological ageing, are predicted by thymic naive CD4+ T cell levels. These data suggest inherited defects of DNA repair may provide valuable insight into physiological ageing. Thymic naive CD4+ T cells may provide a biomarker for vaccine responsiveness in elderly cohorts. (C) 2011 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)26-36
Number of pages11
JournalClinical Immunology
Volume140
Issue number1
DOIs
Publication statusPublished - 1 Jul 2011

Keywords

  • Immune ageing
  • Ataxia telangiectasia
  • Naive T cells
  • T cell receptor
  • Pneumococcal antibodies
  • ATM kinase

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