NK cells are Selleckchem LDK378 some of the early effector cells that respond to an adenovirus infection.14, 15 In the wild-type mice infected with AdCre, the intrahepatic NK cell population remained relatively

stable between postinfection days 7 and 14 in terms of both the percentages (22.2% and 17.4%, respectively) and the absolute numbers (4.1 and 3.2 × 105, respectively; Table 1). Despite the similarity of their percentages (21.5% and 20.0%), the average number of intrahepatic NK cells in the CD40 transgenic mice decreased considerably because of the much contracted IHL pools from days 7 to 14 (from 6.3 to 2.0 × 105). Like other viral infections,16 the AdCre infection resulted in significant declines in the NKT percentages in comparison with the percentages for PBS-injected animals on postinfection days 7 and 14 (Table 1). To test whether hepatic CD40 expression modulated phenotypical changes, cytokine production, and cytotoxicity in IHLs,14 we measured CD40L levels and intracellular IFN-γ in CD8+ and CD4+ T cells ex vivo (Supporting Fig. 5 and Fig. 5). The presence of CD40 on hepatocytes did not change the expression of CD40L in CD4+ T cells in

the liver (Supporting Fig. 5). After the viral infection, higher percentages of CD8+ and CD4+ T cells in the transgenic mice expressed IFN-γ in comparison with those in the uninfected control animals on day 7 (P < 0.05 and P < 0.01, respectively; Fig. 5 and Supporting Fig. 8A). Nearly Sirolimus supplier one half of the CD4+ cells from both transgenic and wild-type mice expressed IFN-γ on postinfection day 14, and there

were no differences between these two groups of cells (Fig. 5). Granzyme B resides in cytotoxic granules and is a key effector molecule of CD8+ CTLs and NK cells.15 To assess the effect of CD40 on granzyme B–mediated target cell destruction, we measured granzyme B–expressing CD8+ T cells and NK cells. Similar percentages of CD8+ cells in the transgenic and control mice expressed granzyme B on postinfection day 7 (Fig. 6 and Supporting Fig. 8B). After a phase of increased apoptosis and population contraction (Fig. 4 and Table 1), however, a small percentage of CTLs (11.3%) produced greater amounts of this lytic molecule, Plasmin as measured by the mean fluorescence intensity (MFI), in the transgenic mice on day 14 (P < 0.05; Fig. 6 and Supporting Fig. 8B). After a similar course of population changes (Fig. 4A, and Table 1), higher percentages of intrahepatic NK cells in the transgenic mice secreted granzyme B on day 14 (P < 0.05; Fig. 6 and Supporting Fig. 8B). Overall, these results suggest that parenchymal CD40 expression can perturb the population dynamics of CTL and NK cells in the liver and alter their effector functions in adenoviral infections. Kupffer cells are the resident macrophages in the liver and are closely situated next to their neighboring hepatocytes.