As expected, neither hepatocytes nor LSECs isolated from nontransgenic mice stimulated COR93-specific CD8+ T cells to express CD69 unless they were first pulsed with COR93-peptide (Figures 7E and 7J, white bars) indicating the antigen specificity of the T cell response to the HBV transgenic hepatocytes. Collectively, these data suggest that www.selleckchem.com/products/ganetespib-sta-9090.html intrahepatic priming of COR93-specific CD8+ T cells was primarily mediated by endogenously synthesized antigen produced by the HBV-transgenic hepatocytes. Figure 6 Intrahepatic accumulation and activation of COR93-specific CD8+ T cells in HBV transgenic mice. Figure 7 Na?ve COR93-specific CD8+ T cells are activated by HBV expressing hepatocytes.

Intrahepatic priming of functionally defective T cell responses is independent of T cell antigen specificity To determine if intrahepatic priming of functionally defective CD8+ T cells is a general rule or restricted to COR93-specific TCR transgenic T cells, we adoptively transferred naive ENV28-specific T cells from CD45.1-6C2.36 TCRtg mice into MHC-matched HBV transgenic mice and nontransgenic littermates. Groups of 3 mice were sacrificed 4 hours, 3 days and 7 days after adoptive transfer to examine the ENV28-specific CD8+ T cell response in the liver (Figure 8; white bars), lymph nodes (Figure 8; gray bars) and spleen (Figure 8, black bars). ENV28-specific na?ve CD8+ T cells were rapidly activated in the liver of the HBV transgenic mouse recipients (but not in nontransgenic recipients �C not shown) as early as 4 hours after adoptive transfer (Figure 8A), suggesting that, like COR93-specific na?ve CD8+ T cells, adoptively transferred ENV28-specific CD8+ na?ve T cells are primed in the liver.

The intrahepatically primed ENV28-specific CD8+ T cells expanded in the liver (Figure 8B), but did not express IFN�� or GrB (Figure 8C and 8D). These results recapitulate the immunological events observed after adoptive transfer of COR93-specific na?ve T cells into HBV transgenic mice illustrated in Figures 2 and and4,4, indicating that intrahepatic T cell priming and the expansion of functionally defective T cells occur irrespective of the antigen specificity or MHC restriction of the T cells. Thus, T cell hyporesponsiveness represents a general outcome induced by intrahepatic T cell priming to endogenously Dacomitinib synthesized hepatocellular antigen. Figure 8 Intrahepatic priming and expansion of functionally defective ENV28-specific CD8+ T cells.