Introduction NKT 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 γδ T cells respond to CD1d induced by infection, causing viral myocarditis.
Methods Model liver and human hepatic immune responses were measured. CD1d reactivity of distinct T cell populations was assayed, compared to total T cell responses.
Results NKT also potentially contribute to chronic Hepatitis C, since human liver-specific γδ Vδ3 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.
Conclusion NKT 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 Interest M. Exley Shareholder of: NKT Therapeutics, Inc.
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