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

• Published in: Blood 2002-08, Vol.100 (3), p.933-940
• Main Authors: Dunne, Padraic J., Faint, Jeffery M., Gudgeon, Nancy H., Fletcher, Jean M., Plunkett, Fiona J., Soares, Maria Vieira D., Hislop, Andrew D., Annels, Nicola E., Rickinson, Alan B., Salmon, Mike, Akbar, Arne N.
• Format: Article
• Language: English
• Subjects: Acute Disease; Antigen Presentation - immunology; Apoptosis - immunology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Division - immunology; Herpesvirus 4, Human - immunology; Human viral diseases; Humans; Immunologic Memory - immunology; Infectious diseases; Infectious Mononucleosis - blood; Infectious Mononucleosis - immunology; Infectious Mononucleosis - virology; Leukocyte Common Antigens - metabolism; Medical sciences; Telomere - ultrastructure; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-01-0160

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.