Defective clearance of adenovirus in IRF-1 mice associated with defects in NK and T cells but not macrophages

Scandinavian Journal of Immunology
X XuJ D Mountz

Abstract

A replication-defective adenovirus-LacZ recombinant virus (AdLacZ) was injected intravenously into IRF-1(-/-) mice and wild-type mice to characterize the contribution of IRF-1 to the immune-mediated clearance of Ad vector. Compared with wild-type mice, IRF-1(-/-) mice expressed higher levels of the LacZ gene product in the liver. After infusion of the AdLacZ, the expression of IRF-1 mRNA was upregulated in the liver of wild-type mice, but not in IRF-1(-/-) mice. Both spleen and liver mononuclear cells from IRF-1(-/-) mice initially exhibited a markedly lower number of NK, NK-T and CD8 T cells. At day 7 after the administration of AdLacZ, there was a significantly increased population of NK, NK-T and CD8 T cells in both spleen and liver, and also CD11b(+) cells in liver of IRF-1(-/-) mice, compared with the increased in wild-type mice. As IRF-1 is an important signal for production of IFN-gamma by CD8 T and NK cells as well as production of IL-12 by CD11b(+) cells, we determined whether there were lower levels of these cytokines in IRF-1(-/-) mice after Ad challenge. Surprisingly, there were lower levels of IL-12, but higher levels of IFN-gamma and IL-18 in IRF-1(-/-) compared with wild-type mice at day 7 after administration wi...Continue Reading

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Citations

Jun 12, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jian ChenJohn D Mountz
Apr 5, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Anton P McCaffreyMark A Kay
Mar 22, 2007·The Journal of General Virology·Peter TomasecGavin W G Wilkinson

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