title: Telomere length dynamics in human memory T cells specific for viruses causing acute or latent infections.
abstract: 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.
authors: Division of Infectious Diseases and Immunology, University of Massachusetts, Medical School, Worcester MA, USA. anuja.mathew@umassmed.edu.
authors: Joel M
authors: JM
authors: O'Bryan
authors: Marcia
authors: M
authors: Woda
authors: Mary
authors: M
authors: Co
authors: Anuja
authors: A
authors: Mathew
authors: Alan L
authors: AL
authors: Rothman
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