Blocking virus replication during acute murine cytomegalovirus infection paradoxically prolongs antigen presentation and increases the CD8+ T cell response by preventing type I IFN-dependent depletion of dendritic cells

Christopher P. Loo, Christopher M. Snyder, Ann Hill

Research output: Contribution to journalArticle

4 Scopus citations


Increasing amounts of pathogen replication usually lead to a proportionate increase in size and effector differentiation of the CD8+ T cell response, which is attributed to increased Ag and inflammation. Using a murine CMV that is highly sensitive to the antiviral drug famciclovir to modulate virus replication, we found that increased virus replication drove increased effector CD8+ T cell differentiation, as expected. Paradoxically, however, increased virus replication dramatically decreased the size of the CD8+ T cell response to two immunodominant epitopes. The decreased response was due to type I IFN-dependent depletion of conventional dendritic cells and could be reproduced by specific depletion of dendritic cells from day 2 postinfection or by sterile induction of type I IFN. Increased virus replication and type I IFN specifically inhibited the response to two immunodominant epitopes that are known to be dependent on Ag cross-presented by DCs, but they did not inhibit the response to "inflationary" epitopes whose responses can be sustained by infected nonhematopoietic cells. Our results show that type I IFN can suppress CD8+ T cell responses to cross-presented Ag by depleting cross-presenting conventional dendritic cells.

Original languageEnglish (US)
Pages (from-to)383-393
Number of pages11
JournalJournal of Immunology
Issue number1
StatePublished - Jan 1 2017


ASJC Scopus subject areas

  • Immunology

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