Negative Regulation of Type I IFN Expression by OASL1 Permits Chronic Viral Infection and CD8+ T-Cell Exhaustion
Figure 6
Effect of early in vivo blockade of IFN-I receptor signaling on viral clearance and virus-specific CD8+ T-cell responses in Oasl1 KO mice.
Mice were infected with LCMV CL-13. At 1.5 d p.i., 0.5 mg IFNAR-1 mAb (αIFNAR-1) or its control isotype Ab (Isotype) was administrated i.v. once into Oasl1 KO mice. PBS was injected into WT mice as another control. (A) Changes in body weight at the indicated time points. (B) Serum virus titers of mice at indicated time points p.i. Vertical arrowhead indicates the time point of antibody injection and dashed black line represents the virus detection limit. (C) Frequencies of virus (GP33 and GP276)-specific CD8+ T cells and their PD-1 expression levels in the spleen at 35 d p.i. Numbers in the plots (left) indicate the percentages of the corresponding cell population among CD8+ T cells. Absolute numbers of GP33 tetramer-positive CD8+ T cells (top right) and PD-1 MFI values for GP33 tetramer-positive CD8+ T cells (bottom right) were also depicted. (D) Cytokine production on CD8+ T cells obtained from spleens at 35 d p.i. after in vitro restimulation with GP33 peptide. Percentages of cytokine-producing cells among CD8+ T cells (left) are shown. Absolute numbers of CD8+ T cells producing IFN-γ (top right) and the frequencies of TNF-α-producing cells among IFN-γ + CD8+ T cells (bottom right) are also depicted. All line graphs and bar graphs show mean ± SD and mean + SD, respectively. Data are representative of two independent experiments (n = 3 per group in each experiment). Statistical significance was determined by comparison between isotype-treated KO mice and each of the other two groups, PBS-treated WT mice or αIFNAR-1-treated KO mice. ns, not significant; *, P<0.05; **, P<0.01; ***, P<0.001.