HBcore-specific CXCR6+CD8 T cells during persistent HBV replication in mice lose their effector function and have high CREM activity

We investigated molecular profiles of CD8 T cells in persistent experimental Hepatitis B virus (HBV) infection. To this end, we established a preclinical in vivo model where HBV-replicating hepatocytes were cleared by virus-specific immunity after infection with 107 IU Ad-HBV, whereas persistent HBV replication developed after infection with 108 IU Ad-HBV, revealed by high serum HBeAg levels, high numbers of HBV genome copies and of HBcorepos hepatocytes in liver tissue. To overcome variable surface expression of the T cell receptor during chronic infection and unequivocally identify HBV-specific CD8 T cells, we adoptively transferred naïve CD45.1+HBcore-specific CD8 T cells from Cor93 transgenic mice (HBcoreCD8 T cells) the day before Ad-HBV infection. After clearance of HBV-replicating hepatocytes (d44 p.i.), liver CD45.1+HBcoreCD8 T cells expressed either CXCR6 or CX3CR1, and in the spleen only CX3CR1+ CD8 T cells were detected. Next, we evaluated the transcriptional profile of FACSorted HBcoreCD8 T cells after resolved compared to persistent infection employing SmartSeq2. The resulting dataset is reported here.