Virus-specific and bystander CD8+ T-cell proliferation in the acute and persistent phases of a gammaherpesvirus infection.

The cycling characteristics of CD8+ T cells specific for two lytic-phase epitopes of murine gammaherpesvirus 68 (gammaHV68) have been analyzed for mice with high or low levels of virus persistence. The extent of cell division is generally reflective of the antigen load and suggests that gammaHV68 may be regularly reactivating from latency for some months after the resolution of the acute phase of the infectious process. Although gammaHV68 infection is also associated with massive proliferation of lymphocytes that are not obviously specific for the virus, the level of "bystander-induced" cycling in a population of influenza virus-specific CD8+ T cells was generally fourfold lower than the extent of cell division seen for the antigen-driven, gammaHV68-specific response. The overall conclusion is that turnover rates substantially in excess of 5 to 10% over 6 days for CD8+ "memory" T-cell populations are likely to be reflective of continued antigenic exposure.