Control Of B Cell Lymphoma By Gammaherpesvirus-Induced Memory Cd8 T Cells

Persistent infection with gammaherpesviruses (gamma HV) can cause lymphomagenesis in immunocompromised patients. Murine gamma HV-68 (MHV-68) is an important tool for understanding immune factors contributing to gamma HV control; however, modeling control of gamma HV-associated lymphomagenesis has been challenging. Current model systems require very long incubation times or severe immune suppression, and tumor penetrance is low. In this report, we describe the generation of a B cell lymphoma on the C57BL/6 background, which is driven by the Myc oncogene and expresses an immunodominant CD8 T cell epitope from MHV-68. We determined MHV-68-specific CD8 T cells in latently infected mice use either IFN-gamma or perforin/granzyme to control gamma HV-associated lymphoma, but perforin/granzyme is a more potent effector mechanism for lymphoma control than IFN-gamma. Consistent with previous reports, CD4-depleted mice lost control of virus replication in persistently infected mice. However, control of lymphoma remained intact in the absence of CD4 T cells. Collectively, these data show the mechanisms of T cell control of B cell lymphoma in gamma HV-infected mice overlap with those necessary for control of virus replication, but there are also important differences. This study establishes a tool for further dissecting immune surveillance against, and optimizing adoptive T cell therapies for, gamma HV-associated lymphomas.