Accumulation of PD-1+ TIGIT+ T cells in the liver after local antigen reactivity and during autoimmune hepatitis
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In autoimmune hepatitis (AIH), hepatocellular damage is linked to an accumulation of autoreactive T cells in the liver of patients, but how these cells emerge in the tissue remains unclear. Here we used a mouse model based on recombination-dependent inducible expression of influenza A hemagglutinin (HA) by hepatocytes to investigate initiation of liver antigen-specific response. Our study revealed that peripheral immunization, unlike inflammatory triggers, is essential to initiate an immune response against a liver antigen. We showed that liver T cell reactivity after peripheral immunization is marked by PD-1 and TIGIT co-expression and that the frequency of PD-1 + TIGIT + HLA-DR + CD38 + CD8 T cells in the blood of AIH patients is associated with liver injury. Our findings suggest a potential influence of the peripheral immunization for the liver-antigen-specific responses during AIH. Liver tissue-activated T cells probably recirculate during active phase of the disease, unveiling potential immunomarkers to monitor disease activity.
Highlights
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Peripheral immunization rather than local inflammation induces an immune response against a hepatic antigen
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PD-1 and TIGIT co-expression by T cells is found after tissue antigen-specific T cell reactivity
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Frequency of circulating PD-1 + TIGIT + HLA-DR + CD38 + CD8 T cells is associated with AIH disease activity
In brief
Guinebretière et al. demonstrate that after peripheral immunization, liver-antigen-specific T cell accumulation in the tissue is marked by local PD-1/TIGIT co-expression, a phenotype shared with liver and circulating T cell subsets enriched in active autoimmune hepatitis (AIH) patients. These findings suggest the influence of peripheral immunization on the initiation of AIH and provide potential immunomarker of AIH activity.
