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) 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.
Plunkett
F J
FJ
Department of Clinical Immunology and Department of Haematology, Royal Free and University College Medical School, London, United Kingdom.
Soares
M V
MV
Annels
N
N
Hislop
A
A
Ivory
K
K
Lowdell
M
M
Salmon
M
M
Rickinson
A
A
Akbar
A N
AN
D000208:Acute Disease; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000648:ultrastructure*; D003116:Color; D005434:Flow Cytometry / Q000379:methods*; D004854:Herpesvirus 4, Human / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007244:Infectious Mononucleosis / Q000235:genetics* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000648:ultrastructure; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D019098:Telomerase