T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss
Authors
Furmanski, Anna L.O'Shaughnessy, Ryan F.L.
Saldana, Jose Ignacio
Blundell, Michael P.
Thrasher, Adrian J.
Sebire, Neil
Davies, E Graham
Crompton, Tessa
Issue Date
2013-01-10
Metadata
Show full item recordAbstract
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 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.Citation
Furmanski 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.Publisher
ElsevierPubMed ID
23303453PubMed Central ID
PMC3631608Additional Links
https://www.sciencedirect.com/science/article/pii/S0022202X15362291Type
ArticleLanguage
enISSN
0022-202Xae974a485f413a2113503eed53cd6c53
10.1038/jid.2012.492
Scopus Count
Collections
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Green - can archive pre-print and post-print or publisher's version/PDF
Related articles
- SCF/c-kit signaling is required for cyclic regeneration of the hair pigmentation unit.
- Authors: Botchkareva NV, Khlgatian M, Longley BJ, Botchkarev VA, Gilchrest BA
- Issue date: 2001 Mar
- Induction of cellular immunity against hair follicle melanocyte causes alopecia.
- Authors: Nagai H, Oniki S, Oka M, Horikawa T, Nishigori C
- Issue date: 2006 Aug
- Despite efficient intrathymic negative selection of host-reactive T cells, autoimmune disease may develop in porcine thymus-grafted athymic mice: evidence for failure of regulatory mechanisms suppressing autoimmunity.
- Authors: Zhao Y, Rodriguez-Barbosa JI, Shimizu A, Sachs DH, Sykes M
- Issue date: 2003 Jun 15
- Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging.
- Authors: Van Neste D, Tobin DJ
- Issue date: 2004
- Delineating immune-mediated mechanisms underlying hair follicle destruction in the mouse mutant defolliculated.
- Authors: Ruge F, Glavini A, Gallimore AM, Richards HE, Thomas CP, O'Donnell VB, Philpott MP, Porter RM
- Issue date: 2011 Mar