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T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss

Furmanski, AL; O'Shaughnessy, RF; Saldana, JI; Blundell, MP; Thrasher, AJ; Sebire, NJ; Davies, EG; (2013) T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss. Journal of Investigative Dermatology , 133 (5) 1221 - 1230. 10.1038/jid.2012.492. Green open access

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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.

Type: Article
Title: T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/jid.2012.492
Publisher version: http://dx.doi.org/10.1038/jid.2012.492
Language: English
Additional information: © 2013 The Society for Investigative Dermatology. This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/. PMCID: PMC3631608
Keywords: Adoptive Transfer, Alopecia, Animals, CD4-Positive T-Lymphocytes, Cell Proliferation, Disease Models, Animal, Hair Color, Hair Follicle, Homeodomain Proteins, Humans, Melanocytes, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Nude, Pigmentation, Thymus Gland, Transplantation, Heterologous, Up-Regulation
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1393813
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