CD94/NKG2A expression is associated with proliferative potential of CD8 T cells during persistent polyoma virus infection

Anthony M. Byers, Nicolas P. Andrews, Aron E. Lukacher

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Memory CD8 T cells comprise a critical component of durable immunity because of their capacity to rapidly proliferate and exert effector activity upon Ag rechallenge. During persistent viral infection, memory CD8 T cells repetitively encounter viral Ag and must maintain a delicate balance between limiting viral replication and minimizing immunopathology. In mice infected by polyoma virus, a natural mouse pathogen that establishes long-term persistent infection, the majority of persistence-phase antiviral CD8 T cells express the inhibitory NK cell receptor CD94/NKG2A. In this study, we asked whether CD94/NKG2A expression is associated with Ag-specific recall of polyoma virus-specific CD8 T cells. During the persistent phase of infection, polyoma virus-specific CD8 T cells that express CD94/NKG2A were found to preferentially proliferate; this proliferation was dependent on cognate Ag both in vitro and in vivo. In addition, CD94/NKG2A+ polyoma-specific CD8 T cells have a markedly enhanced capacity to produce IL-2 upon ex vivo Ag stimulation compared with CD94/NKG2A- polyoma-specific CD8 T cells. Importantly, CD94/NKG2A+ anti-polyoma virus CD8 T cells appear to be essential for Ag-specific recall responses in mice persistently infected by polyoma virus. Because of its higher proliferative potential and capacity to produce IL-2, we propose that the CD94/NKG2A+ subpopulation represents a less differentiated state than the CD94/NKG2A- subpopulation. Identification of proliferation-competent subpopulations of memory CD8 T cells should prove valuable in designing therapeutic vaccination strategies for persistent viral infections.

Original languageEnglish (US)
Pages (from-to)6121-6129
Number of pages9
JournalJournal of Immunology
Volume176
Issue number10
DOIs
StatePublished - May 15 2006

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Polyomavirus
Virus Diseases
T-Lymphocytes
Interleukin-2
Natural Killer Cell Receptors
Infection
Antiviral Agents
Immunity
Vaccination

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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title = "CD94/NKG2A expression is associated with proliferative potential of CD8 T cells during persistent polyoma virus infection",
abstract = "Memory CD8 T cells comprise a critical component of durable immunity because of their capacity to rapidly proliferate and exert effector activity upon Ag rechallenge. During persistent viral infection, memory CD8 T cells repetitively encounter viral Ag and must maintain a delicate balance between limiting viral replication and minimizing immunopathology. In mice infected by polyoma virus, a natural mouse pathogen that establishes long-term persistent infection, the majority of persistence-phase antiviral CD8 T cells express the inhibitory NK cell receptor CD94/NKG2A. In this study, we asked whether CD94/NKG2A expression is associated with Ag-specific recall of polyoma virus-specific CD8 T cells. During the persistent phase of infection, polyoma virus-specific CD8 T cells that express CD94/NKG2A were found to preferentially proliferate; this proliferation was dependent on cognate Ag both in vitro and in vivo. In addition, CD94/NKG2A+ polyoma-specific CD8 T cells have a markedly enhanced capacity to produce IL-2 upon ex vivo Ag stimulation compared with CD94/NKG2A- polyoma-specific CD8 T cells. Importantly, CD94/NKG2A+ anti-polyoma virus CD8 T cells appear to be essential for Ag-specific recall responses in mice persistently infected by polyoma virus. Because of its higher proliferative potential and capacity to produce IL-2, we propose that the CD94/NKG2A+ subpopulation represents a less differentiated state than the CD94/NKG2A- subpopulation. Identification of proliferation-competent subpopulations of memory CD8 T cells should prove valuable in designing therapeutic vaccination strategies for persistent viral infections.",
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CD94/NKG2A expression is associated with proliferative potential of CD8 T cells during persistent polyoma virus infection. / Byers, Anthony M.; Andrews, Nicolas P.; Lukacher, Aron E.

In: Journal of Immunology, Vol. 176, No. 10, 15.05.2006, p. 6121-6129.

Research output: Contribution to journalArticle

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AU - Lukacher, Aron E.

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