Development of mouse models with restricted HLA-B∗57:01 presentation for the study of flucloxacillin-driven T-cell activation and tolerance in liver injury.

ABSTRACT:

Background

Flucloxacillin (FLX)-induced liver injury is immune-mediated and highly associated to HLA-B∗57:01 expression. Host factors leading to drug-induced liver injury are not yet well understood.

Objective

Characterize in vivo immune mechanisms determining the development of CD8⁺ T cells reactive to FLX in animals expressing the risk human leukocyte antigen (HLA) allotype.

Methods

HLA-B∗57:01 transgenic mice (Tg) or Tg strains with H2-K^bD^b knockout (Tg/KO) or H2-K^bD^b/PD-1 double knockout (Tg/DKO) were treated with drug and/or anti-CD4 antibody. Drug-induced liver injury was evaluated on the basis of liver enzyme and histologic changes at day 10 of treatment. FLX-reactive CD8⁺ T cells were characteri

SUBMITTER: Ananthula S 

PROVIDER: S-EPMC10524621 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature