The flow cytometric analysis of telomere length in antigen-specific CD8(+)T cells during acute Epstein-Barr virus infection

Acute infectious mononucleosis (AIM) induced by Epstein-Barr virus (EBV) in fection is characterized by extensive expansion of antigen specific CD8(+) T cells. One potential consequence of this considerable proliferative activ ity is telomere shortening, which predisposes the EBV-specific cells to rep licative senescence. To investigate this, a method was developed that enabl es the simultaneous identification of EBV specificity of the CD8(+) T cells , using major histocompatibility complex (MHC) class I/peptide complexes, t ogether with telomere length, which is determined by fluorescence in situ h ybridization, Despite the considerable expansion, CD8(+) EBV-specific T cel ls in patients with AIM maintain their telomere length relative to CD8(+) T cells in normal individuals and relative to CD4(+) T cells within the pati ents themselves and this is associated with the induction of the enzyme tel omerase, 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 b ut 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 i nitial stages of disease resolution, the capacity of these cells to up-regu late this enzyme after restimulation by the persisting virus may dictate th e extent of telomere maintenance in the memory CD8(+) T-cell pool over time . (C) 2001 by The American Society of Hematology.