Department of Medicine, Division of Infectious Diseases and Immunology
Immunology of Infectious Disease
BACKGROUND: Declining telomere length (TL) is associated with T cell senescence. While TL in naive 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 naive 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.
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Citation: O'Bryan JM, Woda M, Co M, Mathew A, Rothman AL. Telomere length dynamics in human memory T cells specific for viruses causing acute or latent infections. Immun Ageing. 2013 Aug 26;10(1):37. doi: 10.1186/1742-4933-10-37. Link to article on publisher's site
Ageing, Telomere, T cell memory, CD45RA, FlowFISH, Influenza A virus, Cytomegalovirus, Vaccinia virus, Varicella zoster virus, BrdU labeling