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.
Ageing, Telomere, T cell memory, CD45RA, FlowFISH, Influenza A virus, Cytomegalovirus, Vaccinia virus, Varicella zoster virus, BrdU labeling
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Copyright 2013 O'Bryan et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI of Published Version
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
Immunity and ageing : I and A
O'Bryan, Joel M.; Woda, Marcia; Co, Mary Dawn T.; Mathew, Anuja; and Rothman, Alan, "Telomere length dynamics in human memory T cells specific for viruses causing acute or latent infections" (2013). University of Massachusetts Medical School Faculty Publications. 326.