Control of B Cell Lymphoma by Gammaherpesvirus-Induced Memory CD8 T Cells.
J Immunol
; 205(12): 3372-3382, 2020 12 15.
Article
em En
| MEDLINE
| ID: mdl-33188072
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfoma de Células B
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Vírus da Hepatite Murina
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
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Memória Imunológica
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Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article