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

Chabot, Sylvie; Fakhfakh, Amin; Béland, Kathie; Lamarre, Alain; Oldstone, Michael B.A.; Alvarez, Fernando; Djilali-Saiah, Idriss (2013). Mouse liver-specific CD8(+) T-cells encounter their cognate antigen and acquire capacity to destroy target hepatocytes Journal of Autoimmunity , vol. 42 . p. 19-28. DOI: 10.1016/j.jaut.2012.10.002.

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Résumé

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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Mots-clés libres: Autoimmune hepatitis; Autoreactive CD8+ T-cells; Peripheral tolerance mechanisms; Transgenic mouse model
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 01 juin 2017 15:19
Dernière modification: 01 juin 2017 15:19
URI: http://espace.inrs.ca/id/eprint/2874

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