Protective Antigen-Independent CD8 T Cell Memory Is Maintained during γ-Herpesvirus Persistence

Ag persistence during high-titer chronic viral infections induces CD8 T cell dysfunction and lack of Ag-independent CD8 T cell memory formation. However, we have a poor understanding of the generation and maintenance of CD8 T cell memory during asymptomatic persistent viral infections, particularly gamma-herpesvirus infections. In this study, we demonstrate that the continuous presence of cognate Ag in the host is not required for the maintenance of CD8 T cell memory during a persistent gamma-herpesvirus infection. Importantly, the Ag-independent CD8 T cell memory that is maintained during gamma-herpesvirus persistence has the capacity to survive long-term under homeostatic conditions and to mount a protective recall response to a secondary encounter with the pathogen. These data highlight the ability of the immune system to maintain a population of protective memory CD8 T cells with capacity for long-term Ag-independent survival in the presence of systemic virus persistence. The Journal of Immunology, 2009, 132: 3995-4004.