Virus-induced CD8+ T cell clonal expansion is associated with telomerase up-regulation and telomere length preservation: a mechanism for rescue from replicative senescence.
In acute infectious mononucleosis (AIM), very large clones of Ag-specific CD8+ effector T cells are generated. Many clones persist as memory cells, although the clone size is greatly reduced. It would be expected that the large number of cell divisions occurring during clonal expansion would lead to shortening of telomeres, predisposing to replicative senescence. Instead, we show that clonally expanded CD8+ T cells in AIM have paradoxical preservation of telomere length in association with marked up-regulation of telomerase. We postulate that this allows a proportion of responding T cells to enter the memory pool with a preserved capacity to continue dividing so that long-term immunological memory can be maintained.
Maini
M K
MK
Imperial Cancer Research Fund Tumour Immunology Unit, Department of Oncology, University College London Medical School, United Kingdom.
Soares
M V
MV
Zilch
C F
CF
Akbar
A N
AN
Beverley
P C
PC
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000821:virology; D002455:Cell Division / Q000276:immunology; D016922:Cellular Senescence / Q000276:immunology; D002999:Clone Cells / Q000166:cytology / Q000201:enzymology / Q000821:virology; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007244:Infectious Mononucleosis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D019098:Telomerase / Q000096:biosynthesis* / Q000502:physiology; D016615:Telomere / Q000201:enzymology / Q000276:immunology / Q000821:virology; D015854:Up-Regulation / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D019098:Telomerase