title: High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo.
abstract: Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. Using tetrameric complexes of human histocompatibility leukocyte antigen (HLA) class I to identify antigen-specific T cells ex vivo, we observed high frequencies of circulating MelanA-specific, A*0201-restricted cytotoxic T lymphocytes (A2-MelanA tetramer+ CTLs) in seven of nine HLA-A*0201-positive individuals with vitiligo. Isolated A2-MelanA tetramer+ CTLs were able to lyse A*0201-matched melanoma cells in vitro and their frequency ex vivo correlated with extent of disease. In contrast, no A2-MelanA tetramer+ CTL could be identified ex vivo in all four A*0201-negative vitiligo patients or five of six A*0201-positive asymptomatic controls. Finally, we observed that the A2-MelanA tetramer+ CTLs isolated from vitiligo patients expressed high levels of the skin homing receptor, cutaneous lymphocyte-associated antigen, which was absent from the CTLs seen in the single A*0201-positive normal control. These data are consistent with a role of skin-homing autoreactive melanocyte-specific CTLs in causing the destruction of melanocytes seen in autoimmune vitiligo. Lack of homing receptors on the surface of autoreactive CTLs could be a mechanism to control peripheral tolerance in vivo.
authors.affiliation: Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, Oxford, United Kingdom.
authors.forename: G S
authors.initials: GS
authors.lastname: Ogg
authors.forename: P
authors.initials: P
authors.lastname: Rod Dunbar
authors.forename: P
authors.initials: P
authors.lastname: Romero
authors.forename: J L
authors.initials: JL
authors.lastname: Chen
authors.forename: V
authors.initials: V
authors.lastname: Cerundolo
mesh_terms: D000483:Alleles; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008213:Lymphocyte Activation; D008544:Melanocytes / Q000276:immunology*; D008545:Melanoma; D010455:Peptides / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014820:Vitiligo / Q000276:immunology* / Q000473:pathology
chemical_list: D015234:HLA-A Antigens; D010455:Peptides