title: Peripheral and local human papillomavirus 16-specific CD8+ T-cell expansions characterize erosive oral lichen planus.
abstract: Erosive oral lichen planus (OLP) is a chronic, disabling mucocutaneous dysimmune rare disease characterized by mucosal inflammatory erosive lesions with pathological evidence for a marked CD8+ cytotoxic T-lymphocyte (CTL) infiltration. However, the specificity of lesional CTL in OLP has never been analyzed. To investigate the molecular mechanisms underlying dysregulation of T-cell immune responses in patients with OLP, we studied the diversity and antigen specificity of the TCR expressed by CD8+ T cells using dextramer staining, spectratyping, and TCR sequencing in 10 OLP patients undergoing extracorporeal photochemotherapy. Expansions of TCRVβ3-bearing CD8+ T cells were found in peripheral blood and in lesional tissues of OLP patients. Spectratyping and sequencing studies identified specific clonotypes in each patient. These expansions were enriched with human papillomavirus 16 (HPV16)-specific CD8+ T cells in HLA-A*0201+ patients as shown by their immune recognition of the E711-20 immunodominant epitope. Under treatment with extracorporeal photochemotherapy, clonotypic CD8+ T-cell expansions decreased in parallel with clinical remission. Altogether, these data establish a link between HPV infection and OLP pathogenesis by identifying a massive clonal expansion of CD8+ T cells with increased frequency of HPV 16-specific CD8+ T cells in OLP patients.
authors.affiliation: Antiviral Immunity Biotherapy and Vaccine Unit, Institut Pasteur, Paris, France; Sorbonne Paris Cité Université Paris Diderot, Paris, France.
authors.forename: Manuelle
authors.initials: M
authors.lastname: Viguier
authors.affiliation: Sorbonne Paris Cité Université Paris Diderot, Paris, France; Université Paris Descartes, Imagine Institute, Necker Hospital, Paris, France. Electronic address: herve.bachelez@sls.aphp.fr.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bachelez
authors.affiliation: Antiviral Immunity Biotherapy and Vaccine Unit, Institut Pasteur, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Poirier
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; INSERM, U1043, Toulouse, France; CNRS, UMR5282, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Kagan
authors.affiliation: Antiviral Immunity Biotherapy and Vaccine Unit, Institut Pasteur, Paris, France; Université Paris Diderot, UMR-S728, INSERM, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Battistella
authors.affiliation: Service de Dermatologie, Centre Hospitalier Universitaire, SFR FED 4234, EA 3181, Université de Franche Comté, Besançon, France.
authors.forename: François
authors.initials: F
authors.lastname: Aubin
authors.affiliation: UMR 1282 INRA-Université François Rabelais, Tours, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Touzé
authors.affiliation: Laboratoire d'Immunologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Maryvonnick
authors.initials: M
authors.lastname: Carmagnat
authors.affiliation: Service de Dermatologie-Allergologie, Hôpital Tenon, Université Paris VI, AP-HP, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Francès
authors.affiliation: Antiviral Immunity Biotherapy and Vaccine Unit, Institut Pasteur, Paris, France. Electronic address: mlgougeo@pasteur.fr.
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Gougeon
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; INSERM, U1043, Toulouse, France; CNRS, UMR5282, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France. Electronic address: nicolas.fazilleau@inserm.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fazilleau
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D019674:Genes, T-Cell Receptor beta; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D017676:Lichen Planus, Oral / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged