Defective clearance of adenovirus in IRF-1 mice associated with defects in NK and T cells but not macrophages.
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 with AdLacZ. These results indicate that delayed clearance of Ad is associated with partial correction of defects of the NK, NK-T and CD8 T cells and increased production of IFN-gamma and IL-18 in IRF-1(-/-) mice.
Xu
X
X
Department of Medicine, The University of Alabama at Birmingham, 701 S. 19th Street, Birmingham, AL 35294-0007, USA.
Zhang
H-G
HG
Liu
Z-Y
ZY
Wu
Q
Q
Yang
P-A
PA
Sun
S-H
SH
Chen
J
J
Hsu
H-C
HC
Mountz
J D
JD
D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D050856:Interferon Regulatory Factor-1; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000382:microbiology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000473:pathology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012313:RNA