Epstein-Barr virus–specific CD8+ T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential

Open Access
Publisher Website
Google Scholar
Abstract
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.