Cell-mediated immune responses observed after the adoptive transfer of HCV-primed splenocytes in an HCV transgenic mouse model

HCV is a positive stranded RNA virus that infects up to 170 million people worldwide. Chronic infection is established in 80% of the cases and may lead to cirrhosis and hepatocellular carcinomas. A major debate regarding chronic HCV pathogenesis is whether liver damage is host or virus mediated. CD4+ and CD8+ immune responses are needed to control infection but these are often inefficient, resulting in chronic infection. The presence of these responses in chronic infection may contribute to liver pathogenesis. To study the relevance of immune-mediated liver damage, we created an immunization regimen which elicited humoral and cellular immune responses in B6C3F1 mice. HCVprimed donor splenocytes were stained with CFSE and transferred to a CE1E2 HCV Tg mouse model. Donor cells were recovered in various organs eight days following the transfer. HCV-primed CD4+ and CD8+ T cells selectively accumulated in the liver of the Tg mice where the CE1E2 transgene is predominantly expressed and caused liver pathology under the form of lymphocyte infiltration. The accumulation of these cells indicates a homing mechanism to this organ and a role in the development of liver pathologies. Further studies are required to unearth the mechanisms behind cellular trafficking and cell-mediated immune damage. Acknowledgments First and foremost, I would like to thank my supervisor Dr. Francisco DiazMitoma for welcoming me into his lab and for providing me with the opportunity to carry out not only my honour's research but also my master's degree. His enthusiasm, passion, optimism and willingness to teach were essential for the success of this project. I would also like to recognize the guidance of my co-supervisor Dr. Kathryn Wright since I have always thought of her as a role model for women in sciences and was enlightened by her vast knowledge and dedication. I would like to mention Dr. Lionel Filion for giving me wise advice and helping me see the light at the end of the tunnel. I also wish to thank my committee members Dr. Earl Brown, Dr. Kathryn Wright and Dr. Subash Saad for their assistance in the completion of my project, for their critiques and educated advice. Finally, I would also like to thank the lab members Masoud Ghorbani, Turaya Naas, Liz Samayoa, Amine Saad, Simon Dong, Ali Azizi, Rita Frost, Katrina Gee and Sue Aucoin for their guidance and support. I would especially like to thank Catalina Soare for being my mentor: the completion of this project would have been impossible without her guidance. I am indebted to many student colleagues for providing a stimulating environment in which to learn and grow as a student. I am especially grateful to Liz Samayoa, Maria Blahoianu, Katrina Gee, Catalina Soare and Turaya Naas for helping me get through the difficult times, for all the emotional support, friendship and caring they provided, as well as the dark room sessions and the beers. Also, I would like to mention the support of many good friends found outside of the laboratory. I would also like to thank the members of Dr. Ashok Kumar's and Dr. Marko Kryworuchko's laboratories and the workers from Variation Biotechnologies Inc.