Control of B Cell Lymphoma by Gammaherpesvirus-Induced Memory CD8 T Cells
| Autor: | Young-Kwang Usherwood, Bruce R. Branchini, Yina H. Huang, Taewook Kang, Edward J. Usherwood, Nicholas K. Preiss |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Lymphoma
B-Cell viruses T cell Immunology Epitopes T-Lymphocyte Mice Transgenic CD8-Positive T-Lymphocytes Article Epitope Mice 03 medical and health sciences 0302 clinical medicine Immune system hemic and lymphatic diseases medicine Animals Immunology and Allergy Cytotoxic T cell B-cell lymphoma Murine hepatitis virus biology virus diseases biochemical phenomena metabolism and nutrition medicine.disease Neoplasm Proteins Lymphoma medicine.anatomical_structure Granzyme Perforin biology.protein Cancer research Female Immunologic Memory 030215 immunology |
| Zdroj: | J Immunol |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2000734 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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