Control of B Cell Lymphoma by Gammaherpesvirus-Induced Memory CD8 T Cells

• Published in: The Journal of immunology (1950) 2020-12, Vol.205 (12), p.3372-3382
• Main Authors: Preiss, Nicholas K, Kang, Taewook, Usherwood, Young-Kwang, Huang, Yina H, Branchini, Bruce R, Usherwood, Edward J
• Format: Article
• Language: English
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Female; Immunologic Memory; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - immunology; Lymphoma, B-Cell - pathology; Mice; Mice, Transgenic; Murine hepatitis virus - genetics; Murine hepatitis virus - immunology; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2000734

Persistent infection with gammaherpesviruses (γHV) can cause lymphomagenesis in immunocompromised patients. Murine γHV-68 (MHV-68) is an important tool for understanding immune factors contributing to γHV control; however, modeling control of γHV-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-γ or perforin/granzyme to control γHV-associated lymphoma, but perforin/granzyme is a more potent effector mechanism for lymphoma control than IFN-γ. 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 γHV-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, γHV-associated lymphomas.