title: Toward the Clonotype Analysis of Alopecia Areata-Specific, Intralesional Human CD8+ T Lymphocytes.
abstract: Alopecia areata (AA) is an organ-restricted autoimmune disease that mainly affects the hair follicle (HF). Several findings support a key primary effector role of CD8+ T cells in the disease pathogenesis. Autoreactive CD8+ T cells are not only present in the characteristic peribulbar inflammatory cell infiltrate of lesional AA HFs but are also found to be infiltrating in lesional HF epithelium where they are thought to recognize major histocompatibility complex class I-presented (auto-)antigens. However, the latter still remain unidentified. Therefore, one key aim in AA research is to identify the clonotypes of autoaggressive, intralesional CD8+ T cells. Therapeutically, this is important (a) so that these lymphocytes can be selectively eliminated or inhibited, (b) to identify the-as yet elusive-key (auto-)antigens in AA, and/or (c) to induce peripheral tolerance against the latter. Therefore, we have recently embarked on a National Alopecia Areata Foundation-supported project that attempts to isolate disease-specific, intralesional CD8+ T cells from AA skin in order to determine their TCR clonotype, using two complementary strategies. The first method is based on the enzymatic skin digestion from lesional AA skin, followed by either MACS technology and single-cell picking or FACS cell sorting, while the second method on laser microdissection. The identification of disease-specific TCRs can serve as a basis for specific AA immunotherapy along the lines sketched above and may possibly also provide prognostic biomarkers. If successful, this research strategy promises to permit, at long last, the causal therapy of AA.
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Bertolini
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.|Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Uchida
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.|Centre for Dermatology Research, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000506:Alopecia Areata / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology*; D003584:Cytological Techniques; D018859:Hair Follicle / Q000276:immunology / Q000473:pathology; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*
chemical_list: D011948:Receptors, Antigen, T-Cell