Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia

Clin Immunol. 2011 Jul;140(1):26-36. doi: 10.1016/j.clim.2011.03.007. Epub 2011 Mar 13.


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 naïve 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 naïve CD4+ T cell levels. These data suggest inherited defects of DNA repair may provide valuable insight into physiological ageing. Thymic naïve CD4+ T cells may provide a biomarker for vaccine responsiveness in elderly cohorts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / immunology*
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia / immunology*
  • Ataxia Telangiectasia Mutated Proteins
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Count
  • Cell Cycle Proteins / genetics
  • Cell Separation
  • DNA-Binding Proteins / genetics
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Protein-Serine-Threonine Kinases / genetics
  • Tumor Suppressor Proteins / genetics


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases