T-Cell Reconstitution after Thymus Xenotransplantation Induces Hair Depigmentation and Loss
| Autor: | Anna L. Furmanski, José Ignacio Saldaña, Michael P. Blundell, Adrian J. Thrasher, Ryan F.L. O'Shaughnessy, Neil J. Sebire, Tessa Crompton, E. Graham Davies |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer Pathology medicine.medical_specialty T cell medicine.medical_treatment Transplantation Heterologous Mice Nude Thymus Gland Dermatology In Vitro Techniques Biology Biochemistry Mice 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Depigmentation Antigen medicine Animals Humans Hair Color Molecular Biology Cell Proliferation 030304 developmental biology Homeodomain Proteins Mice Knockout Autoimmune disease 0303 health sciences Pigmentation Alopecia Cell Biology Hair follicle medicine.disease Adoptive Transfer Up-Regulation 3. Good health Mice Inbred C57BL Transplantation Disease Models Animal medicine.anatomical_structure Thymus transplantation Melanocytes Original Article medicine.symptom Hair Follicle |
| Zdroj: | The Journal of Investigative Dermatology |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2012.492 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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