FasL and IFNgamma Effects on the CD8+ T cell Response to Hepatocellular Antigen

Immune responses to hepatic pathogens often fail to eliminate invading organisms emphasizing the importance of understanding immune processes in the liver. CD8+ T cells are an important cellular player in the immune system; their activation and effector function are critical for the clearance of pathogens from infected cells. While their activation in the lymph node is well-understood and documented, CD8+ T cell activation in the liver is less familiar and an area of continuing research. This study investigates the mechanism of CD8+ T cells activation in response to hepatocyte-derived antigen and the effect they have on the presence of the RNA and DNA that encodes that antigen. Our lab has developed a mouse model that clarifies this interaction using an Adeno-associated virus to deliver the ovalbumin antigen SIINFEKL to hepatocytes. OT-1 cells, a CD8+ T cell from a transgenic mouse that specifically recognizes SIINFEKL, are then used to study both the activation of these cells in the liver and their effect on vector-transduced hepatocytes. The following thesis describes the role of two molecules, FasL and IFNgamma, in the activation of CD8+ T cells in the liver and the effect of these cells on vector RNA and DNA. The findings indicate that the administration of a near physiologic number of transgenic CD8+ T cells results in prolonged, low-level inflammation but an inability to eliminate vector from the liver. The activation of the CD8+ T cells is optimal when in the presence of Fas:FasL signaling and IFNgamma signaling.