Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia

被引：26

作者：

Exley, Andrew Robert ^{[1
,2
]}

Buckenham, Samantha ^{[1
]}

Hodges, Elizabeth ^{[3
]}

Hallam, Robert ^{[1
]}

Byrd, Phil ^{[4
]}

Last, James ^{[4
]}

Trinder, Claire ^{[1
]}

Harris, Susan ^{[3
]}

Screaton, Nicholas ^{[5
]}

Williams, Anthony P. ^{[6
]}

Taylor, A. Malcolm R. ^{[4
]}

Shneerson, John M. ^{[7
]}

机构：

[1] Cambridge Univ Hlth Partners, Papworth Hosp NHS Fdn Trust, Immunol Lab, Dept Pathol, Cambridge CB23 3RE, England

[2] Cambridge Univ Hlth Partners, Papworth Hosp NHS Fdn Trust, Thorac Dept, Resp Infect Inflammat & Immunol Unit, Cambridge CB23 3RE, England

[3] Southampton Univ Hosp NHS Trust, Southampton SO16 6YD, Hants, England

[4] Univ Birmingham, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England

[5] Cambridge Univ Hlth Partners, Papworth Hosp NHS Fdn Trust, Dept Radiol, Cambridge CB23 3RE, England

[6] Univ Southampton, CR UK Inst Canc Studies, Southampton SO16 6YD, Hants, England

[7] Cambridge Univ Hlth Partners, Papworth Hosp NHS Fdn Trust, Thorac Dept, Resp Support & Sleep Ctr, Cambridge CB23 3RE, England

来源：

CLINICAL IMMUNOLOGY | 2011年 / 140卷 / 01期

关键词：

ATM kinase; Ataxia telangiectasia; Immune ageing; Naive T cells; T cell receptor; Pneumococcal antibodies; T-CELL-RECEPTOR; PNEUMOCOCCAL CONJUGATE VACCINE; STREPTOCOCCUS-PNEUMONIAE; POLYSACCHARIDE VACCINE; DEFICIENT LYMPHOCYTES; OXIDATIVE STRESS; B-LYMPHOCYTE; ATM; MUTATIONS; REPERTOIRE;

D O I：

10.1016/j.clim.2011.03.007

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：26 / 36

页数：11

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