title: Therapeutic implications of autoimmune vitiligo T cells.
abstract: Vitiligo is an autoimmune disease presenting with progressive loss of skin pigmentation. The disease strikes 1% of the world population, generally during teenage years. The progressive loss of melanocytes from depigmenting vitiligo skin is accompanied by cellular infiltrates containing both CD4+ and CD8+ T lymphocytes. Infiltrating cytotoxic T cells with high affinity T cell receptors have likely escaped clonal deletion in the thymus, allowing such T cells to enter the circulation. Through the expression of CLA, these T cells home to the skin where they express type 1-cytokine profiles and mediate melanocyte apoptosis via the granzyme/perforin pathway. T cells found juxtapositionally apposed to remaining melanocytes can be isolated from the skin. Vitiligo T cells have demonstrated reactivity to antigens previously recognized as target antigens for T cells infiltrating melanoma tumors. In a comparison to existing melanoma-derived T cells, vitiligo T cells displayed superior reactivity towards melanoma cells. It is thought that genes encoding the TCRs expressed by vitiligo skin infiltrating T cells can be cloned and expressed in melanoma T cells, thereby generating a pool of circulating T cells with high affinity for their targets that can re-direct the immune response towards the tumor.
authors.affiliation: Department of Pathology/Oncology Institute, Loyola University Chicago, 2160 South First Ave, Bldg 112, Rm 203, Maywood, IL 60153, USA.
authors.forename: Kepa
authors.initials: K
authors.lastname: Oyarbide-Valencia
authors.forename: Jasper G
authors.initials: JG
authors.lastname: van den Boorn
authors.forename: Cecele J
authors.initials: CJ
authors.lastname: Denman
authors.forename: Mingli
authors.initials: M
authors.lastname: Li
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Carlson
authors.forename: Claudia
authors.initials: C
authors.lastname: Hernandez
authors.forename: Michael I
authors.initials: MI
authors.lastname: Nishimura
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Das
authors.forename: Rosalie M
authors.initials: RM
authors.lastname: Luiten
authors.forename: I Caroline
authors.initials: IC
authors.lastname: Le Poole
mesh_terms: D000818:Animals; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014820:Vitiligo / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell