TY - JOUR
T1 - Epstein-Barr virus-specific CD8(+) T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential
AU - Dunne, PJ
AU - Faint, Jeffrey
AU - Gudgeon, Nancy
AU - Fletcher, J
AU - Plunkett, FJ
AU - Scares, MVD
AU - Hislop, Andrew
AU - Annels, NE
AU - Rickinson, Alan
AU - Salmon, Michael
AU - Akbar, Ali
PY - 2002/8/1
Y1 - 2002/8/1
N2 - 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 pep-tide. 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.
AB - 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 pep-tide. 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.
UR - http://www.scopus.com/inward/record.url?scp=0036682492&partnerID=8YFLogxK
U2 - 10.1182/blood-2002-01-0160
DO - 10.1182/blood-2002-01-0160
M3 - Article
C2 - 12130505
SN - 1528-0020
VL - 100
SP - 933
EP - 940
JO - Blood
JF - Blood
IS - 3
ER -