Telomere length dynamics in human memory T cells specific for viruses causing acute or latent infections

Immunity & Ageing

Alan L Rothman¹  Anuja Mathew²  Mary Co²  Marcia Woda²  Joel M O'Bryan² 

[1] Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, USA;Division of Infectious Diseases and Immunology, University of Massachusetts, Medical School, Worcester MA, USA

关键词: BrdU labeling;    Varicella zoster virus;    Vaccinia virus;    Cytomegalovirus;    Influenza A virus;    FlowFISH;    CD45RA;    T cell memory;    Telomere;    Ageing;   

Others  :  814207
DOI  :  10.1186/1742-4933-10-37

 received in 2013-01-30, accepted in 2013-08-21,  发布年份 2013

【 摘 要 】

Background

Declining telomere length (TL) is associated with T cell senescence. While TL in naïve and memory T cells declines with increasing age, there is limited data on TL dynamics in virus-specific memory CD4⁺ T cells in healthy adults. We combined BrdU-labeling of virus-stimulated T cells followed with flow cytometry-fluorescent in situ hybridization for TL determination. We analyzed TL in T cells specific for several virus infections: non-recurring acute (vaccinia virus, VACV), recurring-acute (influenza A virus, IAV), and reactivating viruses (varicella-zoster virus, VZV, and cytomegalovirus, CMV) in 10 healthy subjects. Additionally, five subjects provided multiple blood samples separated by up to 10 years.

Results

VACV- and CMV-specific T cells had longer average TL than IAV-specific CD4⁺ T cells. Although most virus-specific cells were CD45RA^-, we observed a minor population of BrdU+ CD45RA⁺ T cells characterized by long telomeres. Longitudinal analysis demonstrated a slow decline in average TL in virus-specific T cells. However, in one subject, VZV reactivation led to an increase in average TL in VZV-specific memory T cells, suggesting a conversion of longer TL cells from the naïve T cell repertoire.

Conclusions

TLs in memory CD4⁺ T cells in otherwise healthy adults are heterogeneous and follow distinct virus-specific kinetics. These findings suggests that the distribution of TL and the creation and maintenance of long TL memory T cells could be important for the persistence of long-lived T cell memory.

【 授权许可】

   
2013 O'Bryan et al.; licensee BioMed Central Ltd.

【 图 表 】

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