T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss
AuthorsFurmanski, Anna L.
O'Shaughnessy, Ryan F.L.
Saldana, Jose Ignacio
Blundell, Michael P.
Thrasher, Adrian J.
Davies, E Graham
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AbstractHere 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 tissueinto 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.
CitationFurmanski AL, O'Shaughnessy RFL, Saldana JI, Blundell MP, Thrasher AJ, Sebire NJ, Davies EG, Crompton T (2013) 'T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss', Journal of Investigative Dermatology, 133 (5), pp.1211-1230.
PubMed Central IDPMC3631608
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- Creative Commons
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