title: Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients.
abstract: In vitiligo, cytotoxic T cells infiltrating the perilesional margin are suspected to be involved in the pathogenesis of the disease. However, it remains to be elucidated whether these T cells are a cause or a consequence of the depigmentation process. T cells we obtained from perilesional skin biopsies, were significantly enriched for melanocyte antigen recognition, compared with healthy skin-infiltrating T cells, and were reactive to melanocyte antigen-specific stimulation. Using a skin explant model, we were able to dissect the in situ activities of perilesional T cells in the effector phase of depigmentation. We show that these T cells could infiltrate autologous normally pigmented skin explants and efficiently kill melanocytes within this microenvironment. Interestingly, melanocyte apoptosis was accompanied by suprabasal keratinocyte apoptosis. Perilesional T cells did, however, not induce apoptosis in lesional skin, which is devoid of melanocytes, indicating the melanocyte-specific cytotoxic activity of these cells. Melanocyte killing correlated to local infiltration of perilesional T cells. Our data show that perilesional cytotoxic T cells eradicate pigment cells, the characteristic hallmark of vitiligo, thereby providing evidence of T cells being able to mediate targeted autoimmune tissue destruction.
authors.affiliation: Department of Dermatology, Netherlands Institute for Pigment Disorders, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jasper G
authors.initials: JG
authors.lastname: van den Boorn
authors.forename: Debby
authors.initials: D
authors.lastname: Konijnenberg
authors.forename: Trees A M
authors.initials: TA
authors.lastname: Dellemijn
authors.forename: J P Wietze
authors.initials: JP
authors.lastname: van der Veen
authors.forename: Jan D
authors.initials: JD
authors.lastname: Bos
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Florry A
authors.initials: FA
authors.lastname: Vyth-Dreese
authors.forename: Rosalie M
authors.initials: RM
authors.lastname: Luiten
mesh_terms: D017209:Apoptosis; D015551:Autoimmunity; D003602:Cytotoxicity, Immunologic; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology; D008213:Lymphocyte Activation; D008544:Melanocytes / Q000276:immunology / Q000473:pathology*; D012867:Skin / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D014820:Vitiligo / Q000209:etiology / Q000276:immunology* / Q000473:pathology
chemical_list: D020381:Interleukin-17