Plunkett, FJ and Soares, MVD and Annels, N and Hislop, A and Ivory, K and Lowdell, M and Salmon, M and Rickinson, A and Akbar, AN (2001) The flow cytometric analysis of telomere length in antigen-specific CD8(+) T cells during acute Epstein-Barr virus infection. BLOOD , 97 (3) 700 - 707.
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Acute infectious mononucleosis (AIM) induced by Epstein-Barr virus (EBV) infection is characterized by extensive expansion of antigen specific CD8(+) T cells. One potential consequence of this considerable proliferative activity is telomere shortening, which predisposes the EBV-specific cells to replicative senescence. To investigate this, a method was developed that enables the simultaneous identification of EBV specificity of the CD8(+) T cells, using major histocompatibility complex (MHC) class I/peptide complexes, together with telomere length, which is determined by fluorescence in situ hybridization, Despite the considerable expansion, CD8(+) EBV-specific T cells in patients with AIM maintain their telomere length relative to CD8(+) T cells in normal individuals and relative to CD4(+) T cells within the patients themselves and this is associated with the induction of the enzyme telomerase, In 4 patients who were studied up to 12 months after resolution of AIM, telomere lengths of EBV-specific CD8(+) T cells were unchanged in 3 but shortened in one individual, who was studied only 5 months after initial onset of infection. Substantial telomere shortening in EBV-specific CD8(+) T cells was observed in 3 patients who were studied between 15 months and 14 years after recovery from AIM. Thus, although telomerase activation may preserve the replicative potential of EBV-specific cells in AIM and after initial stages of disease resolution, the capacity of these cells to up-regulate this enzyme after restimulation by the persisting virus may dictate the extent of telomere maintenance in the memory CD8(+) T-cell pool over time. (C) 2001 by The American Society of Hematology.
|Title:||The flow cytometric analysis of telomere length in antigen-specific CD8(+) T cells during acute Epstein-Barr virus infection|
|Keywords:||IN-VIVO, REPLICATIVE SENESCENCE, VIRAL-INFECTIONS, SHORTENED TELOMERES, CUTTING EDGE, APOPTOSIS, MEMORY, EXPRESSION, CD28, ACTIVATION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Infection and Immunity (Division of) > Research Department of Immunology|
UCL > School of Life and Medical Sciences > SLMS Planning and Performance Unit > SLMS Research Support Centre > Platform Technologies
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