title: T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss.
abstract: Here we present a mouse model for T-cell targeting of hair follicles, linking the pathogenesis of alopecia to that of depigmentation disorders. Clinically, thymus transplantation has been successfully used to treat T-cell immunodeficiency in congenital athymia, but is associated with autoimmunity. We established a mouse model of thymus transplantation by subcutaneously implanting human thymus tissue into athymic C57BL/6 nude mice. These xenografts supported mouse T-cell development. Surprisingly, we did not detect multiorgan autoimmune disease. However, in all transplanted mice, we noted a striking depigmentation and loss of hair follicles. Transfer of T cells from transplanted nudes to syngeneic black-coated RAG(-/-) recipients caused progressive, persistent coat-hair whitening, which preceded patchy hair loss in depigmented areas. Further transfer experiments revealed that these phenomena could be induced by CD4+ T cells alone. Immunofluorescent analysis suggested that Trp2+ melanocyte-lineage cells were decreased in depigmented hair follicles, and pathogenic T cells upregulated activation markers when exposed to C57BL/6 melanocytes in vitro, suggesting that these T cells are not tolerant to self-melanocyte antigens. Our data raise interesting questions about the mechanisms underlying tissue-specific tolerance to skin antigens.
authors.affiliation: Immunobiology Unit, Institute of Child Health, University College London, London, UK.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Furmanski
authors.forename: Ryan F L
authors.initials: RF
authors.lastname: O'Shaughnessy
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Saldana
authors.forename: Michael P
authors.initials: MP
authors.lastname: Blundell
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sebire
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
authors.forename: Tessa
authors.initials: T
authors.lastname: Crompton
mesh_terms: D019264:Adoptive Transfer; D000505:Alopecia / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology* / Q000502:physiology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006200:Hair Color / Q000502:physiology*; D018859:Hair Follicle / Q000473:pathology / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008544:Melanocytes / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D010858:Pigmentation / Q000502:physiology*; D013950:Thymus Gland / Q000637:transplantation*; D014183:Transplantation, Heterologous; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein