Journal article
Epitope specificity of memory CD8+ T cells dictates vaccination‐induced mortality in LCMV‐infected perforin‐deficient mice
European journal of immunology, Vol.42(6), pp.1488-1499
06/2012
DOI: 10.1002/eji.201142263
PMCID: PMC3650624
PMID: 22678903
Abstract
Perforin‐deficient (PKO) mice serve as models for familial hemophagocytic lympho‐histiocytosis, a uniformly fatal disease associated with viral infection of perforin‐deficient humans. Naïve perforin‐deficient BALB/c mice survive while vaccinated PKO mice containing virus‐specific memory CD8+ T cells rapidly succumb to lymphocytic choriomeningitis virus (LCMV) infection. Thus, vaccination converts a nonlethal persistent infection into a fatal disease mediated by virus‐specific memory CD8+ T cells. Here, we determine the extent to which vaccination‐induced mortality in PKO mice following LCMV challenge is due to differences in vaccine modalities, the quantity or epitope specificity of memory CD8+ T cells. We show that LCMV‐induced mortality in immune PKO mice is independent of vaccine modalities and that the starting number of memory CD8+ T cells specific to the immunodominant epitope NP118‐126 dictates the magnitude of secondary CD8+ T‐cell expansion, the inability to regulate production of CD8+ T‐cell‐derived IFN‐γ, and mortality in the vaccinated PKO mice. Importantly, mortality is determined by the epitope specificity of memory CD8+ T cells and the associated degree of functional exhaustion and cytokine dysregulation but not the absolute magnitude of CD8+ T‐cell expansion. These data suggest that deeper understanding of the parameters that influence the outcome of vaccine‐induced diseases would aid rational vaccine design to minimize adverse outcomes after infection.
Details
- Title: Subtitle
- Epitope specificity of memory CD8+ T cells dictates vaccination‐induced mortality in LCMV‐infected perforin‐deficient mice
- Creators
- Nhat‐Long L Pham - University of IowaVladimir P Badovinac - University of IowaJohn T Harty - University of Iowa
- Resource Type
- Journal article
- Publication Details
- European journal of immunology, Vol.42(6), pp.1488-1499
- DOI
- 10.1002/eji.201142263
- PMID
- 22678903
- PMCID
- PMC3650624
- ISSN
- 0014-2980
- eISSN
- 1521-4141
- Number of pages
- 12
- Grant note
- NIH (AI46653; AI150073; AI42767)
- Language
- English
- Date published
- 06/2012
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047797402771
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