CD4+ T cell help has an epitope-dependent impact on CD8 + T cell memory inflation during murine cytomegalovirus infection

Christopher M. Snyder, Andrea Loewendorf, Elizabeth L. Bonnett, Michael Croft, Chris A. Benedict, Ann B. Hill

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8+ T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4+ T cells have been implicated in maintaining the function and/or number of CD8+ T cells in other chronic infections. Moreover, CD4+ T cells are essential for complete control of MCMV. Thus, we wondered whether CD4+ T cell deficiency would result in impaired MCMV-specific CD8+ T cell responses. Here we show that CD4+ T cell deficiency had an epitope-specific impact on CD8 + T cell memory inflation. Of the three codominant T cell responses during chronic infection, only accumulation of the late-appearing IE3-specific CD8+ T cells was substantially impaired in CD4+ T cell-deficient mice. Moreover, the increased viral activity did not drive increased CD8+ T cell division or substantial dysfunction in any MCMV-specific population that we studied. These data show that CD4+ T cell help is needed for inflation of a response that develops only during chronic infection but is otherwise dispensable for the steady state maintenance and function of MCMV-specific CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)3932-3941
Number of pages10
JournalJournal of Immunology
Issue number6
StatePublished - Sep 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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