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Journal articles

Mouse liver-specific CD8(+) T-cells encounter their cognate antigen and acquire capacity to destroy target hepatocytes.

Abstract : CD8(+) T-cell immune response to liver antigens is often functionally diminished or absent. This may occur via deletion of these autoaggressive T-cells, through the acquisition of an anergic phenotype, or via active suppression mediated by other cell populations. We generated a double transgenic model in which mice express CD8(+) T-cells specific for the lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) and LCMV-NP as a hepatic neo-autoantigen, to study the immunological response of potentially liver antigen autoaggressive CD8(+) T-cells. Autoreactive transgenic CD8(+) T-cells were analyzed for functionality and cytotoxic effector status. Despite severe peripheral deletion of liver-specific CD8(+) T-cells, a fraction of autoreactive NP-specific CD8(+) T-cells accumulate in liver, resulting in hepatocyte injury and production of auto-antibodies in both male and female mice. NP-specific intrahepatic T-cells showed capacity to proliferate, produce cytokines and up-regulate activation markers. These data provide in vivo evidence that autoreactive CD8(+) T-cells are activated in the liver and developed an inflammatory process, but require additional factors to cause severe autoimmune destruction of hepatocytes. Our new model will provide a valuable tool for further exploration of the immunological response involved in inflammatory liver diseases, including autoimmune hepatitis.
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Submitted on : Monday, June 16, 2014 - 8:07:53 PM
Last modification on : Monday, October 8, 2018 - 5:44:05 PM
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Sylvie Chabot, Amin Fakhfakh, Kathie Béland, Alain Lamarre, Michael B A Oldstone, et al.. Mouse liver-specific CD8(+) T-cells encounter their cognate antigen and acquire capacity to destroy target hepatocytes.. Journal of Autoimmunity, Elsevier, 2013, 42, pp.19-28. ⟨10.1016/j.jaut.2012.10.002⟩. ⟨pasteur-01007579⟩



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