Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection

Haina Shin, Shawn D. Blackburn, Joseph Blattman, E. John Wherry

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Efficient maintenance of memory CD8 T cells is central to long-term protective immunity. IL-7- and IL-15-driven homeostatic proliferation is essential for long-term memory CD8 T cell persistence after acute infections. During chronic infections, however, virus-specific CD8 T cells respond poorly to these cytokines. Yet, virus-specific CD8 T cells often persist for long periods of time during chronic infections. We have addressed this apparent paradox by examining the mechanism for maintaining virus-specific CD8 T cells during chronic infection. We find that homeostatic cytokines (e.g., IL-7/15), inflammatory signals, and priming of recent thymic emigrants are not sufficient to maintain virus-specific CD8 T cells over time during chronic infection. Rather, our results demonstrate that viral peptide is required for virus-specific CD8 T cell persistence during chronic infection. Moreover, this viral antigen-dependent maintenance results in a dramatically different type of T cell division than is normally observed during memory T cell homeostasis. Rather than undergoing slow, steady homeostatic turnover during chronic viral infection, CD8 T cells undergo extensive peptide-dependent division, yet cell numbers remain relatively stable. These results indicate that antigen-specific CD8 T cell responses during persisting infection are maintained by a mechanism distinct from that after acute infection. JEM

Original languageEnglish (US)
Pages (from-to)941-949
Number of pages9
JournalJournal of Experimental Medicine
Volume204
Issue number4
DOIs
StatePublished - Apr 16 2007
Externally publishedYes

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Viral Antigens
Viruses
T-Lymphocytes
Infection
Interleukin-15
Interleukin-7
Virus Diseases
Maintenance
Cytokines
CD8 Antigens
Peptides
Long-Term Memory
Cell Division
Immunity
Homeostasis
Cell Count

ASJC Scopus subject areas

  • Immunology

Cite this

Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection. / Shin, Haina; Blackburn, Shawn D.; Blattman, Joseph; Wherry, E. John.

In: Journal of Experimental Medicine, Vol. 204, No. 4, 16.04.2007, p. 941-949.

Research output: Contribution to journalArticle

Shin, Haina ; Blackburn, Shawn D. ; Blattman, Joseph ; Wherry, E. John. / Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 4. pp. 941-949.
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