Epstein-Barr virus-specific CD8(+) T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential.
During acute infection, latent and lytic Epstein-Barr virus (EBV) epitope-specific CD8(+) T cells have a CD45RO(+) CD45RA(-) phenotype. However, after resolution of the infection, a large proportion of these cells, particularly those specific for lytic viral epitopes, re-express the CD45RA molecule. The role of CD8(+) CD45RA(+) T cells in ongoing immunity to EBV and other viruses is unknown. We now demonstrate that, relative to their CD45RO(+) counterparts, the EBV-specific CD8(+) T cells that revert to CD45RA expression after acute infectious mononucleosis are not in cell cycle, have longer telomeres, and are more resistant to apoptosis partly because of increased Bcl-2 expression. However, the EBV-specific CD8(+) CD45RA(+) T cells have shorter telomeres than the total CD8(+) CD45RA(+) T-cell pool and predominantly express low levels of the CCR7 chemokine receptor, indicating that they are not naive cells. In addition, EBV-specific CD8(+) CD45RA(+) T cells can be induced to proliferate and exhibit potent cytotoxic activity against target cells loaded with specific peptide. Our results strongly suggest, therefore, that EBV-specific CD8(+) CD45RA(+) T cells represent a stabilized virus-specific memory pool and not terminally differentiated effector cells. The identification of mechanisms that enable stable virus-specific CD8(+) T cells to persist after acute infection may lead to the enhancement of antiviral immunity in immunocompromised and elderly persons.
Dunne
Padraic J
PJ
Department of Clinical Immunology, Royal Free and University College Medical School, London, United Kingdom.
Faint
Jeffery M
JM
Gudgeon
Nancy H
NH
Fletcher
Jean M
JM
Plunkett
Fiona J
FJ
Soares
Maria Vieira D
MV
Hislop
Andrew D
AD
Annels
Nicola E
NE
Rickinson
Alan B
AB
Salmon
Mike
M
Akbar
Arne N
AN
D000208:Acute Disease; D017951:Antigen Presentation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002455:Cell Division / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007244:Infectious Mononucleosis / Q000097:blood / Q000276:immunology / Q000821:virology; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure
D017493:Leukocyte Common Antigens