Late priming and variability of epitope-specific CD8+ T cell responses during a persistent virus infection.

Abstract

Control of persistently infecting viruses requires that antiviral CD8(+) T cells sustain their numbers and effector function. In this study, we monitored epitope-specific CD8(+) T cells during acute and persistent phases of infection by polyoma virus, a mouse pathogen that is capable of potent oncogenicity. We identified several novel polyoma-specific CD8(+) T cell epitopes in C57BL/6 mice, a mouse strain highly resistant to polyoma virus-induced tumors. Each of these epitopes is derived from the viral T proteins, nonstructural proteins produced by both productively and nonproductively (and potentially transformed) infected cells. In contrast to CD8(+) T cell responses described in other microbial infection mouse models, we found substantial variability between epitope-specific CD8(+) T cell responses in their kinetics of expansion and contraction during acute infection, maintenance during persistent infection, as well as their expression of cytokine receptors and cytokine profiles. This epitope-dependent variability also extended to differences in maturation of functional avidity from acute to persistent infection, despite a narrowing in TCR repertoire across all three specificities. Using a novel minimal myeloablation-bone marrow chimera approach, we visualized priming of epitope-specific CD8(+) T cells during persistent virus infection. Interestingly, epitope-specific CD8(+) T cells differed in CD62L-selectin expression profiles when primed in acute or persistent phases of infection, indicating that the context of priming affects CD8(+) T cell heterogeneity. In summary, persistent polyoma virus infection both quantitatively and qualitatively shapes the antiviral CD8(+) T cell response.

• Authors: Christopher C Kemball, Eun D Han Lee, Vaiva Vezys, Thomas C Pearson, Christian P Larsen, Aron E Lukacher
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 12 Pg. 7950-60 (Jun 15 2005) ISSN: 0022-1767 [Print] United States
• PMID: 15944301 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes, T-Lymphocyte
• Immunodominant Epitopes

Topics

• Animals
• Bone Marrow Transplantation (immunology, methods)
• CD8-Positive T-Lymphocytes (immunology, metabolism, pathology, virology)
• Cell Differentiation (immunology)
• Cell Line, Tumor
• Chimera (genetics, immunology)
• Epitopes, T-Lymphocyte (immunology)
• Female
• Immunodominant Epitopes (immunology)
• Immunologic Memory (genetics)
• Immunophenotyping
• Mice
• Mice, Congenic
• Mice, Inbred C57BL
• Mice, Knockout
• Polyomavirus (immunology)
• Polyomavirus Infections (genetics, immunology, pathology)
• T-Lymphocyte Subsets (immunology, pathology, virology)
• Tumor Virus Infections (genetics, immunology, pathology)
• Virus Latency (genetics, immunology)