Journal Article

LB-004Balance Of Roles For Distinct Cd1d-reactive 'nkt' Cell Populations In Th1-type Anti-viral And Th2 Pro-fibrotic Responses In Viral Hepatitis

Exley, M

2014

Overview

IntroductionNKT can enhance anti-pathogen and anti-tumour immunity via NK and DC, leading to T/B cell activation. Th1-biassed NKT can contribute to protective responses against cancer and viruses. However, NKT can contribute to immunopathology in chronic infections. Patient NKT defects are reversible in vitro, so we are investigating correcting such defects in models and clinic.NKT are required for optimal resistance to certain viruses. Mice lacking all NKT are impaired in lymphocyte activation and in picornavirus clearance. Conversely to acute infection, chronic viral stimulation of NKT can lead to immunopathology. CD1d-specific gamma delta T cells respond to CD1d induced by infection, causing viral myocarditis.MethodsModel liver and human hepatic immune responses were measured. CD1d reactivity of distinct T cell populations was assayed, compared to total T cell responses.ResultsNKT also potentially contribute to chronic Hepatitis C, since human liver-specific gamma delta V delta 3 T cells were CD1d-reactive. CD1d is up-regulated by HCV and high level hepatic CD1d-reactive NKT produce pro-inflammatory Th1 cytokines in chronic hepatitis C and their Type 2 responses increase in cirrhosis.ConclusionNKT in Chronic Hepatitis C, instead of being protective, may promote inflammation and fibrosis while suppressing anti-tumour responses: their inhibition might have clinical utility.Disclosure of InterestM. Exley Shareholder of: NKT Therapeutics, Inc.

• Subject: Hepatitis C virus / Picornavirus