{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:34:24Z","timestamp":1790836464989,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that is believed to be driven by a CD4+ T cell response to liver Ags. However, the pathogenic function of CD4+ effector T cells in AIH is not fully understood. To characterize liver-infiltrating lymphocytes in AIH, we determined the cytokine production of infiltrating cells obtained from biopsy material by quantitative RT-PCR and flow cytometry. A cytokine quantitiative RT-PCR array of AIH specimens revealed that TNF was the most strongly upregulated cytokine, as compared with control livers. To confirm this finding, we determined the frequencies of TNF-producing CD4+ T cells in peripheral blood and in liver biopsy specimens in comparison with those of CD4+ T cells producing IFN-\u03b3 or IL-17. In AIH, TNF-producing CD4+ T cells were significantly expanded, both in blood and liver, whereas IL-17\u2013producing CD4+ T cells were not. However, the majority of the TNF-producing CD4+ T cells in AIH also produced IFN-\u03b3, suggesting that TNF producers might represent a pathogenic activation state of Th1 cells. Ag-specific stimulation of PBMC from AIH patients with the AIH-associated autoantigen SEPSECS resulted in significant TNF production only in patients manifesting SLA\/LP autoantibodies targeting SEPSEC but not in healthy individuals who do not manifest this reactivity. Taken together, our findings indicated that TNF-producing CD4+ T cells are expanded in AIH, both in blood and in liver. TNF-producing CD4+ T cells in AIH seem to be aberrantly activated Th1 cells. Our findings provide a rationale for therapeutic efforts using TNF blockade in AIH.<\/jats:p>","DOI":"10.4049\/jimmunol.1900124","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T22:26:57Z","timestamp":1572906417000},"page":"3148-3156","source":"Crossref","is-referenced-by-count":53,"title":["TNF-Producing Th1 Cells Are Selectively Expanded in Liver Infiltrates of Patients with Autoimmune Hepatitis"],"prefix":"10.1093","volume":"203","author":[{"given":"Claudia S","family":"Bovensiepen","sequence":"first","affiliation":[{"name":"Department of Medicine I, University Medical Centre Hamburg-Eppendorf , 20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Schakat","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University Medical Centre Hamburg-Eppendorf , 20246 Hamburg 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,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-8105","authenticated-orcid":false,"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery and Transplantation, University Medical Centre Hamburg-Eppendorf , 20246 Hamburg ,","place":["Germany"]},{"name":"Department of General, Visceral and Thoracic Surgery, University Medical Centre Hamburg-Eppendorf , 20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9585-7864","authenticated-orcid":false,"given":"Lara","family":"Henze","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University Medical Centre Hamburg-Eppendorf , 20246 Hamburg 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