Stimulation of enhanced CD8 T cell responses following immunization with a hyper-antigen secreting intracytosolic bacterial pathogen

Megan J. Smithey, Suzanne Brandt, Nancy E. Freitag, Darren E. Higgins, H. G.Archie Bouwer

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The intracytosolic niche for replication of Listeria monocytogenes (Lm) facilitates delivery of bacteria-derived Ags into the MHC class I pathway for subsequent stimulation of CD8 effector T cells. Using Lm strains that are equivalent for in vivo virulence yet express marked differences in the level of secretion of a protective target Ag, we have evaluated how these specific differences in secretion levels influences the magnitude and effector function of Ag-specific CD8 T cell responses following Lm injection. Immunization with low doses of a hyperantigen-secreting Lm strain stimulated enhanced target-Ag specific CD8 T cell responses compared with the magnitude stimulated following immunization with the same dose of wild-type Lm. The enhanced determinant-specific response was also evident by in vivo CTL activity, increased numbers of memory cells 4 wk following immunization, and enhanced antilisterial protection following a challenge infection. Initiation of antibiotic treatment 24 h following infection with wild-type Lm markedly reduced the magnitude of the effector CD8 T cell response. In contrast, antibiotic treatment initiated 24 h following immunization with the hyperantigen secreting strain of Lm did not impact the frequency of the target-Ag specific CD8 T cells. Thus, immunization with a low dose of a hyperantigen secreting Lm strain, followed by antibiotic treatment to limit the extent of the infection, may represent a safe strategy for the stimulation of enhanced effector CD8 T cell responses to specific Ag by a rLm vaccine.

Original languageEnglish (US)
Pages (from-to)3406-3416
Number of pages11
JournalJournal of Immunology
Volume180
Issue number5
DOIs
StatePublished - Mar 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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