CD8+ T cells specific to a single Yersinia pseudotuberculosis epitope restrict bacterial replication in the liver but fail to provide sterilizing immunity

Haiqian Shen, Norberto Gonzalez-Juarbe, Krystle Blanchette, Gregory Crimmins, Molly A. Bergman, Ralph R. Isberg, Carlos J. Orihuela, Peter H. Dube

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

CD8+ T cells use contact-dependent cytolysis of target cells to protect the host against intracellular pathogens. We have previously shown that CD8+ T cells and perforin are required to protect against the extracellular pathogen Yersinia pseudotuberculosis. Here we establish an experimental system where CD8+ T cells specific to a single model antigen are the only memory response present at time of challenge. Using mice immunized with a vaccine strain of Listeria monocytogenes that expresses secreted ovalbumin (Lm-OVA), we show that OVA-specific CD8+ T cells are generated and provide limited protection against challenge with virulent OVA+ Y. pseudotuberculosis. Perforin expression by OVA-specific CD8+ T cells was required, as Lm-OVA-immunized perforin-deficient mice showed higher bacterial burden as compared to Lm-OVA-immunized perforin-sufficient mice. Surprisingly, antigen-specific T cell protection waned over time, as Lm-OVA-immune mice eventually succumbed to Yersinia infection. Kinetic analysis of infection in mice with and without OVA-specific CD8+ T cells revealed that bacterial numbers increased sharply in OVA-naïve mice until death, while OVA-immune mice held bacterial burden to a lower level throughout the duration of illness until death. Clonal analysis of bacterial populations in OVA-naïve and OVA-immune mice at distinct time points revealed equivalent and severe bottle-neck effects for bacteria in both sets of mice immediately after intravenous challenge, demonstrating a dominant role for other aspects of the immune system regardless of CD8+ T cell status. These studies indicate that CD8+ T cells against a single antigen can restrict Y. pseudotuberculosis colonization in a perforin-dependent manner, but ultimately are insufficient in their ability to provide sterilizing immunity and protect against death.

Original languageEnglish (US)
Pages (from-to)289-296
Number of pages8
JournalInfection, Genetics and Evolution
Volume43
DOIs
StatePublished - Sep 1 2016

Keywords

  • Bottle-neck
  • CD8 T cells
  • Ovalbumin
  • Perforin
  • Yersinia pseudotuberculosis
  • YopE

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Microbiology (medical)
  • Infectious Diseases

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