Induction of specific T-cell tolerance by adenovirus-transfected, Fas ligand-producing antigen-presenting cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1998-11

AUTHORS

Huang-Ge Zhang, Di Liu, Yuji Heike, PingAr Yang, Zheng Wang, Xiaoyun Wang, David T. Curiel, Tong Zhou, John D. Mountz

ABSTRACT

A major problem associated with adenovirus gene therapy is the T cell-mediated immune response, which is elicited by inoculation of the adenovirus vector and leads to rapid clearance of the virus and loss of transgene expression. In this study, the immune response to adenovirus was prevented by induction of specific T-cell tolerance by pretreatment with adenovirus-infected antigen-presenting cells (APC) that express Fas ligand. Compared with control-treated mice, the tolerized mice showed prolonged expression of lacZ upon administration of AdCMVlacZ 1 week after tolerance induction. In contrast to the control mice, the tolerized mice did not display proliferation of CD3+ T cells in the spleen in response to AdCMVlacZ. Tolerance induction also was indicated by the lower production of interferon-g and interleukin-2 by peripheral T cells isolated from AdCMVlacZ-challenged tolerized mice than by AdCMVlacZ-challenged control-treated mice. The T-cell tolerance was specific for the adenovirus as the T-cell responses to irrelative murine cytomegalovirus remained unimpaired. Our results indicate that adenovirus-specific T-cell tolerance can be induced by APCs that coexpress Fas ligand and adenovirus antigens. We propose that this new strategy can be used to induce tolerance to adenovirus vector gene therapy with resultant prolonged expression of the transgene. More... »

PAGES

1045-1049

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/3488

DOI

http://dx.doi.org/10.1038/3488

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051953130

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9831033


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