Mouse liver-specific CD8(+) T-cells encounter their cognate antigen and acquire capacity to destroy target hepatocytes. - Archive ouverte HAL Access content directly
Journal Articles Journal of Autoimmunity Year : 2013

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

(1, 2) , (1) , (1) , (3) , (4) , (1, 2, 5) , (1)
1
2
3
4
5

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.
Embargoed file
Embargoed file
Ne sera jamais visible
Loading...

Dates and versions

pasteur-01007579 , version 1 (16-06-2014)

Identifiers

Cite

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, 2013, 42, pp.19-28. ⟨10.1016/j.jaut.2012.10.002⟩. ⟨pasteur-01007579⟩

Collections

RIIP INRS-IAF
53 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More