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Protective Antigen-Independent CD8 T Cell Memory Is Maintained during -Herpesvirus Persistence¹

Stephanie S. Cush^* and Emilio Flaño^2,*,

^* Center for Vaccines and Immunity, Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205; and Ohio State University College of Medicine, Columbus, OH 43210

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 -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 -herpesvirus infection. Importantly, the Ag-independent CD8 T cell memory that is maintained during -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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Grant AI-59603 and by the Research Institute.

² Address correspondence and reprint requests to Dr. Emilio Flaño, Center for Vaccines and Immunity, Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205. E-mail address: Emilio.flano{at}nationwidechildrens.org

³ Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; HV68, murine -herpesvirus-68; MLN, mediastinal lymph node; ORF, open reading frame.