Belz, Gabrielle T.;
Stevenson, Philip G.;
Castrucci, Maria R.;
Altman, John D.;
Doherty, Peter C.
Postexposure vaccination massively increases the prevalence of γ-herpesvirus-specific CD8+T cells but confers minimal survival advantage on CD4-deficient mice
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Media type:
E-Article
Title:
Postexposure vaccination massively increases the prevalence of γ-herpesvirus-specific CD8+T cells but confers minimal survival advantage on CD4-deficient mice
Contributor:
Belz, Gabrielle T.;
Stevenson, Philip G.;
Castrucci, Maria R.;
Altman, John D.;
Doherty, Peter C.
imprint:
Proceedings of the National Academy of Sciences, 2000
Published in:Proceedings of the National Academy of Sciences
Language:
English
DOI:
10.1073/pnas.040575197
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
<jats:p>Mice that lack CD4<jats:sup>+</jats:sup>T cells remain clinically normal for more than 60 days after respiratory challenge with the murine γ-herpesvirus 68 (γHV-68), then develop symptoms of a progressive wasting disease. The γHV-68-specific CD8<jats:sup>+</jats:sup>T cells that persist in these I-A<jats:sup>b−/−</jats:sup>mice are unable to prevent continued, but relatively low level, virus replication. Postexposure challenge with recombinant vaccinia viruses expressing γHV-68 lytic cycle epitopes massively increased the magnitude of the γHV-68-specific CD8<jats:sup>+</jats:sup>population detectable by staining with tetrameric complexes of MHC class I glycoprotein + peptide, or by interferon-γ production subsequent to<jats:italic>in vitro</jats:italic>restimulation with peptide. The boosting effect was comparable for γHV-68-infected I-A<jats:sup>b−/−</jats:sup>and I-A<jats:sup>b+/+</jats:sup>mice within 7 days of challenge, and took more than 110 days to return to prevaccination levels in the I-A<jats:sup>b+/+</jats:sup>controls. Although the life-span of the I-A<jats:sup>b−/−</jats:sup>mice was significantly increased, there was no effect on long-term survival. A further boost with a recombinant influenza A virus failed to improve the situation. Onset of weight loss was associated with a decline in γHV-68-specific CD8<jats:sup>+</jats:sup>T cell numbers, though it is not clear whether this was a cause or an effect of the underlying pathology. Even very high levels of virus-specific CD8<jats:sup>+</jats:sup>T cells thus provide only transient protection against the uniformly lethal consequences of γHV-68 infection under conditions of CD4<jats:sup>+</jats:sup>T cell deficiency.</jats:p>