Author(s): Carrozzo M; Pilli M; Penna A; Zerbini A; Vescovi P; Manfredi M; Negro F; Mori C; Giuberti T; Ferrari C; Missale G
Abstract: Hepatitis C virus infection can be associated with different extrahepatic manifestations, including lichen planus; however, no clear role for HCV in their pathogenesis has been established. T cells were isolated from lichen biopsy specimens of 7 HCV positive patients with oral lichen planus. HCV-specific CD4(+) T-cell lines were obtained in 4 patients from lichen lesions but only in 2 of them from the peripheral blood. Different clonal populations were found in oral tissue and peripheral blood of individual patients, as shown by TCR-Vbeta analysis of antigen-specific T cells. Frequency of HCV-specific CD8(+) cells tested with 4 different HCV tetramers was significantly higher in the lichen tissue than in the circulation; moreover, lichen-derived HCV-specific CD8(+) T cells showed the phenotype of recently activated T cells because most of them were CD69(+) and produced interferon gamma (IFN-gamma) but expanded poorly in vitro upon antigen stimulation. The specificity of HCV-reactive T-cell recruitment into the lichen tissue was further confirmed by the absence of HBV-specific T cells within lichen lesions in 3 additional patients with lichen planus associated with HBV infection. Our study shows HCV-specific T-cell responses at the site of the lesions of an HCV-associated dermatologic disease, sustained by HCV-specific T cells with phenotypic and functional characteristics of terminally differentiated effector cells. In conclusion, this finding and the detection of HCV RNA strands in the lichen tissue strongly suggest a role for HCV-specific T-cell responses in the pathogenesis of oral lichen planus associated with HCV infection.
Notes: Journal Article
Keywords: Antibody Specificity CD4-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Cytokines/immunology Hepacivirus/genetics/ immunology Hepatitis C Antigens/immunology Hepatitis C, Chronic/ complications/ immunology Humans Immunophenotyping Lichen Planus, Oral/ etiology/immunology/ virology RNA, Viral/analysis Research Support, Non-U.S. Gov't
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Professor Marco Carrozzo
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