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Epitope specificity of memory CD8+ T cells dictates vaccination-induced mortality in LCMV-infected perforin-deficient mice.
- Source :
- European Journal of Immunology; Jun2012, Vol. 42 Issue 6, p1488-1499, 12p
- Publication Year :
- 2012
-
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 <superscript>+</superscript> 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 <superscript>+</superscript> 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<superscript>+</superscript> 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 <superscript>+</superscript> T cells specific to the immunodominant epitope NP<subscript>118-126</subscript> dictates the magnitude of secondary CD8 <superscript>+</superscript> T-cell expansion, the inability to regulate production of CD8<superscript>+</superscript> T-cell-derived IFN-γ, and mortality in the vaccinated PKO mice. Importantly, mortality is determined by the epitope specificity of memory CD8 <superscript>+</superscript> T cells and the associated degree of functional exhaustion and cytokine dysregulation but not the absolute magnitude of CD8 <superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00142980
- Volume :
- 42
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- European Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 76444652
- Full Text :
- https://doi.org/10.1002/eji.201142263