{"doi":"10.1101/2025.08.29.672936","title":"Accumulation of PD-1+ TIGIT+ T cells in the liver after local antigen reactivity and during autoimmune hepatitis","abstract":"Summary 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 Peripheral immunization rather than local inflammation induces an immune response against a hepatic antigen PD-1 and TIGIT co-expression by T cells is found after tissue antigen-specific T cell reactivity 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":574225,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1004479,"name":"Anaïs Cardon","orcid":"0000-0003-4650-6632","position":1,"is_corresponding":false},{"id":1004808,"name":"Jean‐Paul Judor","orcid":null,"position":2,"is_corresponding":false},{"id":1481655,"name":"Pierre-Jean Gavlovsky","orcid":"0000-0001-5736-5711","position":3,"is_corresponding":false},{"id":1482021,"name":"Fanny Roux","orcid":null,"position":4,"is_corresponding":false},{"id":1481656,"name":"Virginie Huchet","orcid":"0000-0002-5615-3781","position":5,"is_corresponding":false},{"id":1481657,"name":"Caroline Chevalier","orcid":"0000-0002-5210-2020","position":6,"is_corresponding":false},{"id":1482022,"name":"Marion Khaldi","orcid":null,"position":7,"is_corresponding":false},{"id":1020034,"name":"Edouard Bardou‐Jacquet","orcid":"0000-0002-0784-0710","position":8,"is_corresponding":false},{"id":1481658,"name":"Laure Elkrief","orcid":"0000-0003-2843-1710","position":9,"is_corresponding":false},{"id":1482023,"name":"Adrien Lannes","orcid":null,"position":10,"is_corresponding":false},{"id":1481659,"name":"Christine Silvain","orcid":"0000-0002-0712-8491","position":11,"is_corresponding":false},{"id":1481660,"name":"Matthieu Schnee","orcid":"0000-0001-6152-405X","position":12,"is_corresponding":false},{"id":1482024,"name":"Florence Tanné","orcid":null,"position":13,"is_corresponding":false},{"id":1037252,"name":"Sara Lemoinne","orcid":"0000-0001-6947-2709","position":14,"is_corresponding":false},{"id":1016895,"name":"Eléonora De Martin","orcid":"0000-0002-4938-7678","position":15,"is_corresponding":false},{"id":1192755,"name":"Fabienne Vavasseur","orcid":"0000-0002-0531-4354","position":16,"is_corresponding":false},{"id":1004481,"name":"Arnaud Nicot","orcid":"0000-0003-2695-3304","position":17,"is_corresponding":false},{"id":513336,"name":"Sophie Brouard","orcid":"0000-0002-6398-1315","position":18,"is_corresponding":false},{"id":1481661,"name":"Jean‐François Mosnier","orcid":"0000-0003-2637-3641","position":19,"is_corresponding":false},{"id":1481662,"name":"Jérôme Gournay","orcid":"0000-0002-9160-9369","position":20,"is_corresponding":false},{"id":1004482,"name":"Sophie Conchon","orcid":"0000-0003-2602-3385","position":21,"is_corresponding":false},{"id":1004483,"name":"Amédée Renand","orcid":"0000-0003-2265-549X","position":22,"is_corresponding":false},{"id":1004809,"name":"Thomas Guinebretière","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:57:40.686992Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}