The evolution of antigen-specific CD8+ T cell responses after natural primary infection of humans with Epstein-Barr virus

Epstein-Barr virus (EBV) is a persistent, gamma-herpes virus that infects 90% of the human population. Primary infection, particularly if it is delayed until adolescence or beyond, may cause acute infectious mononucleosis and persistent infection may be associated with the development of several malignancies. CD8(+) T cells play a critical role in controlling both the primary and persistent phases of infection. This review summarises work that has been done characterising the primary immune responses to EBV. It goes on to describe the down regulation of the primary immune response and to discuss some of the factors that may be involved in determining the death or survival of populations of antigen-specific CD8+ T cells. Finally it describes features of the populations of memory cells that mediate the long-term control of EBV in healthy seropositive individuals. The studies show differences in the responses to epitopes from lytic cycle versus latent proteins and highlight the complexity of naturally occurring, in vivo, immune responses. A clear understanding of the means by which CD8+ T cells control EBV is important if we are to successfully develop vaccines and other forms of immunotherapy for the virus and its related malignancies.