Hepatitis C virus-specific CD4+ T cell response after liver transplantation occurs early, is multispecific, compartmentalizes to the liver, and does not correlate with recurrent disease.
The role of hepatitis C virus (HCV)-specific CD4+ T cells in recurrent HCV infection after orthotopic liver transplantation (OLTx) is unclear. In parallel, 73 intrahepatic and 73 blood-derived T cell lines were established from 34 patients. At a single cell level, virus-specific interferon (IFN)-gamma production to various HCV proteins was determined by ELISPOT assay: 45 (62%) of 73 liver- or blood-derived T cell lines produced IFN-gamma in response to one of the HCV antigens. HCV specificity was detected mainly in the liver (47% vs. 23% in the blood; P<.05, chi(2) test) and was detectable earlier (< or =6 months) significantly more often than later (>6 months) after OLTx (78% vs 49%; P<.05, chi(2) test). Histology, histologic activity index, liver enzymes, and virus load did not correlate with the occurrence of HCV-specific CD4+ T cells. Despite strong immunosuppressive treatment, OLTx recipients can develop an early, multispecific, preferentially intrahepatic CD4+ T cell response that decreases over time, making it a potential candidate target for novel therapeutic approaches in the transplant setting.
Department of Medicine II, Klinikum Grosshadern, University of Munich, Marchioninstrasse 15, D-81377 Munich, Germany. schirren@med2.med.uni-muenchen.de
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Schirren
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Jung
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Worzfeld
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Mamin
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Baretton
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Gerlach
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Gruener
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Zachoval
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Houghton
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Rau
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D000917:Antibody Formation; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000601:surgery; D018937:Hepatitis C Antibodies / Q000032:analysis / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000276:immunology; D017093:Liver Failure / Q000209:etiology / Q000601:surgery; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D013997:Time Factors
D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D007371:Interferon-gamma