Primary adenovirus-specific cytotoxic T lymphocyte response occurs after viral clearance and liver enzyme elevation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-04-07

AUTHORS

J Chen, A J Zajac, S A McPherson, H-C Hsu, P Yang, Q Wu, X Xu, X Wang, K Fujihashi, D T Curiel, J D Mountz

ABSTRACT

The virus-specific cytotoxic T lymphocyte (CTL) response is a major obstacle to effective delivery of adenovirus gene therapy. However, its relative role in viral clearance, transgene elimination and hepatotoxicity remains unclear. In this paper, we present an analysis of viral clearance and liver toxicity in relation to the induction of the virus-specific CD8 T-cell response revealed by an MHC class I tetramer. A surprisingly high number of tetramer+ CD8 T cells were found in the liver and lung and reached peak values at days 8 and 10, respectively, post-infection. Nearly 100% of these tetramer+ CD8 T cells expressed high levels of granzyme B and IFNγ. Remarkably, liver viral load and liver enzyme elevation peaked early, at days 2 and 4, respectively, post-infection, before the specific CTL response was detectable. After generation of CTLs, there was only minimal liver damage or further decrease in virus titer. These results indicated that the primary peak response of tetramer+ CTLs does not correlate with the elimination of adenovirus or liver cytotoxic response. More... »

PAGES

1079-1088

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gt.3302494

DOI

http://dx.doi.org/10.1038/sj.gt.3302494

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002590237

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15815704


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