Early virus-associated bystander events affect the fitness of the CD8 T cell response to persistent virus infection

Nicolas P. Andrews, Christopher D. Pack, Vaiva Vezys, Glen N. Barber, Aron E. Lukacher

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Chronic Ag exposure during persistent viral infection erodes virus-specific CD8 T cell numbers and effector function, with a concomitant loss of pathogen control. Less clear are the respective contributions of Ag-specific and Ag-nonspecific (bystander) events on the quantity, quality, and maintenance off antiviral CD8 T cells responding to persistent virus infection. In this study, we show that low-dose inoculation with mouse polyomavirus (PyV) elicits a delayed, but numerically equivalent, antiviral CD8 T cell response compared with high-dose inoculation. Low-dose infection generated virus-specific CDS T cells endowed with multicytokine functionality and a superior per cell capacity to produce IFN-γ. PyV-specific CDS T cells primed by low-dose inoculation also expressed higher levels of IL-7Rα and bcl-2 and possessed enhanced Ag-independent survival. Importantly, the quantity and quality of the antiviral CD8 T cell response elicited by dendritic cell-mediated immunization were mitigated by infection with a mutant PyV lacking the dominant CD8 T cell viral epitope. These findings suggest that the fitness of the CDS T cell response to persistent virus infection is programmed in large part by early virus-associated Ag-nonspecific factors, and imply that limiting bystander inflammation at the time of inoculation, independent of Ag load, may optimize adaptive immunity to persistent viral infection.

Original languageEnglish (US)
Pages (from-to)7267-7275
Number of pages9
JournalJournal of Immunology
Volume178
Issue number11
DOIs
Publication statusPublished - Jun 1 2007

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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