期刊
CLINICAL IMMUNOLOGY
卷 140, 期 1, 页码 26-36出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2011.03.007
关键词
ATM kinase; Ataxia telangiectasia; Immune ageing; Naive T cells; T cell receptor; Pneumococcal antibodies
类别
资金
- Papworth Hospital NHS Foundation Trust
- Southampton University Hospitals
- Ataxia Telangiectasia Society
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.
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