Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection

Michael Munks, Kathy S. Cho, Amelia K. Pinto, Sophie Sierro, Paul Klenerman, Ann Hill

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

CMVs are β herpesviruses that establish lifelong latent infection of their hosts. Acute infection of C57BL/6 mice with murine CMV elicits a very broad CD8 T cell response, comprising at least 24 epitopes from 18 viral proteins. In contrast, we show here that the CD8 T cell response in chronically infected mice was dominated by only five epitopes. Altogether, four distinct CD8 T cell kinetic patterns were evident. Responses to some epitopes, including M45, which dominates the acute response, contracted sharply after day 7 and developed into stable long-term memory. The response to m139 underwent rapid expansion and contraction, followed by a phase of memory inflation, whereas the response to an M38 epitope did not display any contraction phase. Finally, responses against two epitopes encoded by the immediate early gene IE3 were readily detectable in chronically infected mice but near the limit of detection during acute infection. CD8 T cells specific for the noninflationary M45 epitope displayed a classic central memory phenotype, re-expressing the lymph node homing receptor CD62L and homeostatic cytokine receptors for IL-7 and IL-15, and produced low levels of EL-2. Responses to two inflationary epitopes, m139 and IE3, retained an effector memory surface phenotype (CD62Llow, IL-7Rα-, IL-15Rβ-) and were unable to produce IL-2. We suggest that immunological choices are superimposed on altered viral gene expression profiles to determine immunodominance during chronic murine CMV infection.

Original languageEnglish (US)
Pages (from-to)450-458
Number of pages9
JournalJournal of Immunology
Volume177
Issue number1
StatePublished - Jul 1 2006

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Muromegalovirus
Cytomegalovirus Infections
Epitopes
T-Lymphocytes
Infection
Lymphocyte Homing Receptors
Phenotype
Interleukin-15
Interleukin-7
Cytokine Receptors
Immediate-Early Genes
Viral Genes
Long-Term Memory
Herpesviridae
Economic Inflation
Viral Proteins
Inbred C57BL Mouse
Transcriptome
Interleukin-2
Limit of Detection

ASJC Scopus subject areas

  • Immunology

Cite this

Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection. / Munks, Michael; Cho, Kathy S.; Pinto, Amelia K.; Sierro, Sophie; Klenerman, Paul; Hill, Ann.

In: Journal of Immunology, Vol. 177, No. 1, 01.07.2006, p. 450-458.

Research output: Contribution to journalArticle

Munks, Michael ; Cho, Kathy S. ; Pinto, Amelia K. ; Sierro, Sophie ; Klenerman, Paul ; Hill, Ann. / Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection. In: Journal of Immunology. 2006 ; Vol. 177, No. 1. pp. 450-458.
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