Oral lichen planus pathogenesis: A role for the HCV-specific cellular immune response.
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.
Pilli
Massimo
M
Divisione Malattie Infettive ed Epatologia, Azienda Ospedaliera Universitaria di Parma, Parma, Italy. missale@tin.it
Penna
Amalia
A
Zerbini
Alessandro
A
Vescovi
Paolo
P
Manfredi
Maddalena
M
Negro
Francesco
F
Carrozzo
Marco
M
Mori
Cristina
C
Giuberti
Tiziana
T
Ferrari
Carlo
C
Missale
Gabriele
G
D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D017676:Lichen Planus, Oral / Q000209:etiology* / Q000276:immunology / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis
D016207:Cytokines; D018936:Hepatitis C Antigens; D012367:RNA, Viral