CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion

Jarad J. Wilson, Christopher D. Pack, Eugene Lin, Elizabeth L. Frost, Joshua A. Albrecht, Annette Hadley, Amelia R. Hofstetter, Satvir S. Tevethia, Todd Schell, Aron Lukacher

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Repetitive Ag encounter, coupled with dynamic changes in Ag density and inflammation, imparts phenotypic and functional heterogeneity to memory virus-specific CD8 T cells in persistently infected hosts. For herpesvirus infections, which cycle between latency and reactivation, recent studies demonstrate that virus-specific T cell memory is predominantly derived from naive precursors recruited during acute infection. Whether functional memory T cells to viruses that persist in a nonlatent, low-level infectious state (smoldering infection) originate from acute infection-recruited naive T cells is not known. Using mouse polyomavirus (MPyV) infection, we previously showed that virus-specific CD8 T cells in persistently infected mice are stably maintained and functionally competent; however, a sizeable fraction of these memory T cells are short-lived. Further, we found that naive anti-MPyV CD8 T cells are primed de novo during persistent infection and contribute to maintenance of the virus-specific CD8 T cell population and its phenotypic heterogeneity. Using a new MPyV-specific TCR-transgenic system, we now demonstrate that virus-specific CD8 T cells recruited during persistent infection possess multicytokine effector function, have strong replication potential, express a phenotype profile indicative of authentic memory capability, and are stably maintained. In contrast, CD8 T cells recruited early in MPyV infection express phenotypic and functional attributes of clonal exhaustion, including attrition from the memory pool. These findings indicate that naive virus-specific CD8 T cells recruited during persistent infection contribute to preservation of functional memory against a smoldering viral infection.

Original languageEnglish (US)
Pages (from-to)4340-4348
Number of pages9
JournalJournal of Immunology
Volume188
Issue number9
DOIs
StatePublished - May 1 2012

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Polyomavirus Infections
T-Lymphocytes
Viruses
Infection
Polyomavirus
Herpesviridae Infections
Virus Diseases

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Wilson, J. J., Pack, C. D., Lin, E., Frost, E. L., Albrecht, J. A., Hadley, A., ... Lukacher, A. (2012). CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion. Journal of Immunology, 188(9), 4340-4348. https://doi.org/10.4049/jimmunol.1103727
Wilson, Jarad J. ; Pack, Christopher D. ; Lin, Eugene ; Frost, Elizabeth L. ; Albrecht, Joshua A. ; Hadley, Annette ; Hofstetter, Amelia R. ; Tevethia, Satvir S. ; Schell, Todd ; Lukacher, Aron. / CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion. In: Journal of Immunology. 2012 ; Vol. 188, No. 9. pp. 4340-4348.
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abstract = "Repetitive Ag encounter, coupled with dynamic changes in Ag density and inflammation, imparts phenotypic and functional heterogeneity to memory virus-specific CD8 T cells in persistently infected hosts. For herpesvirus infections, which cycle between latency and reactivation, recent studies demonstrate that virus-specific T cell memory is predominantly derived from naive precursors recruited during acute infection. Whether functional memory T cells to viruses that persist in a nonlatent, low-level infectious state (smoldering infection) originate from acute infection-recruited naive T cells is not known. Using mouse polyomavirus (MPyV) infection, we previously showed that virus-specific CD8 T cells in persistently infected mice are stably maintained and functionally competent; however, a sizeable fraction of these memory T cells are short-lived. Further, we found that naive anti-MPyV CD8 T cells are primed de novo during persistent infection and contribute to maintenance of the virus-specific CD8 T cell population and its phenotypic heterogeneity. Using a new MPyV-specific TCR-transgenic system, we now demonstrate that virus-specific CD8 T cells recruited during persistent infection possess multicytokine effector function, have strong replication potential, express a phenotype profile indicative of authentic memory capability, and are stably maintained. In contrast, CD8 T cells recruited early in MPyV infection express phenotypic and functional attributes of clonal exhaustion, including attrition from the memory pool. These findings indicate that naive virus-specific CD8 T cells recruited during persistent infection contribute to preservation of functional memory against a smoldering viral infection.",
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Wilson, JJ, Pack, CD, Lin, E, Frost, EL, Albrecht, JA, Hadley, A, Hofstetter, AR, Tevethia, SS, Schell, T & Lukacher, A 2012, 'CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion', Journal of Immunology, vol. 188, no. 9, pp. 4340-4348. https://doi.org/10.4049/jimmunol.1103727

CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion. / Wilson, Jarad J.; Pack, Christopher D.; Lin, Eugene; Frost, Elizabeth L.; Albrecht, Joshua A.; Hadley, Annette; Hofstetter, Amelia R.; Tevethia, Satvir S.; Schell, Todd; Lukacher, Aron.

In: Journal of Immunology, Vol. 188, No. 9, 01.05.2012, p. 4340-4348.

Research output: Contribution to journalArticle

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AU - Wilson, Jarad J.

AU - Pack, Christopher D.

AU - Lin, Eugene

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Wilson JJ, Pack CD, Lin E, Frost EL, Albrecht JA, Hadley A et al. CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion. Journal of Immunology. 2012 May 1;188(9):4340-4348. https://doi.org/10.4049/jimmunol.1103727