Liver international : official journal of the International Association for the Study of the Liver · 2026
Intrahepatic Tissue-Resident CD8+ T-Cell Programmes Associate With Fibrosis and Local Immune Remodelling in Autoimmune Hepatitis.
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Stary Victoria, Losek Sarah, Mairinger Magdalena, Prager Gerhard, Santol Jonas, Starlinger Patrick P, Reiberger Thomas, Stättermayer Albert F, Stary Georg
Аннотация
BACKGROUND AND AIMS: Autoimmune hepatitis is an immune-mediated liver disease characterized by chronic inflammation and progressive fibrosis. Tissue-resident memory T cells mediate organ-specific immunity, but their role in autoimmune hepatitis remains poorly understood. We characterized tissue-residency-associated T-cell populations and their cytokine profiles, assessed associations with disease severity and determined whether these signatures were reflected in peripheral blood.
METHODS: Paired blood and liver samples were obtained from 19 patients with autoimmune hepatitis. Comparator cohorts included 20 patients with metabolic dysfunction-associated steatotic liver disease and 20 surgical patients providing non-inflamed adjacent non-tumorous liver tissue. Multiparameter flow cytometry assessed tissue-residency markers, T-cell differentiation and cytokine production after polyclonal stimulation. Immune phenotypes were correlated with histological and clinical parameters.
RESULTS: Autoimmune hepatitis was associated with compartment-specific remodelling of T-cell differentiation states and intrahepatic enrichment of CD8+ T cells expressing CD69, CD103 and CXCR6 relative to paired blood and comparator liver tissues. Intrahepatic CD8+ T cells exhibited an interferon-γ-dominant cytokine profile, whereas CD4+ T cells showed broader interferon-γ-, interleukin-17A- and interleukin-4-associated responses. Despite the enrichment of tissue-residency-associated CD8+ T cells, cytokine-producing CD8+ T-cell populations with and without a tissue-resident memory phenotype contributed comparably to the hepatic T-cell compartment. Tissue-residency-associated phenotypes correlated positively with Ishak fibrosis stage, whereas the frequency of interferon-γ-positive intrahepatic CD8+ T cells correlated inversely with fibrosis.
CONCLUSIONS: Autoimmune hepatitis was characterized by intrahepatic accumulation of phenotypically distinct and functionally active CD8+ tissue-resident memory T cells associated with fibrosis. This immune profile was not reflected in paired blood, indicating compartmentalized hepatic immune remodelling.
METHODS: Paired blood and liver samples were obtained from 19 patients with autoimmune hepatitis. Comparator cohorts included 20 patients with metabolic dysfunction-associated steatotic liver disease and 20 surgical patients providing non-inflamed adjacent non-tumorous liver tissue. Multiparameter flow cytometry assessed tissue-residency markers, T-cell differentiation and cytokine production after polyclonal stimulation. Immune phenotypes were correlated with histological and clinical parameters.
RESULTS: Autoimmune hepatitis was associated with compartment-specific remodelling of T-cell differentiation states and intrahepatic enrichment of CD8+ T cells expressing CD69, CD103 and CXCR6 relative to paired blood and comparator liver tissues. Intrahepatic CD8+ T cells exhibited an interferon-γ-dominant cytokine profile, whereas CD4+ T cells showed broader interferon-γ-, interleukin-17A- and interleukin-4-associated responses. Despite the enrichment of tissue-residency-associated CD8+ T cells, cytokine-producing CD8+ T-cell populations with and without a tissue-resident memory phenotype contributed comparably to the hepatic T-cell compartment. Tissue-residency-associated phenotypes correlated positively with Ishak fibrosis stage, whereas the frequency of interferon-γ-positive intrahepatic CD8+ T cells correlated inversely with fibrosis.
CONCLUSIONS: Autoimmune hepatitis was characterized by intrahepatic accumulation of phenotypically distinct and functionally active CD8+ tissue-resident memory T cells associated with fibrosis. This immune profile was not reflected in paired blood, indicating compartmentalized hepatic immune remodelling.