Late Priming and Variability of Epitope-Specific CD8+ T Cell Responses during a Persistent Virus Infection

• Published in: The Journal of immunology (1950) Vol. 174; no. 12; pp. 7950 - 7960
• Main Authors: Kemball, Christopher C, Lee, Eun D. Han, Vezys, Vaiva, Pearson, Thomas C, Larsen, Christian P, Lukacher, Aron E
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-06-2005
• Subjects: Animals; Bone Marrow Transplantation - immunology; Bone Marrow Transplantation - methods; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - virology; Cell Differentiation - immunology; Cell Line, Tumor; Chimera - genetics; Chimera - 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; Polyomavirus Infections - immunology; Polyomavirus Infections - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology; T-Lymphocyte Subsets - virology; Tumor Virus Infections - genetics; Tumor Virus Infections - immunology; Tumor Virus Infections - pathology; Virus Latency - genetics; Virus Latency - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.12.7950

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.