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J Invest Dermatol. 2014 May;134(5):1285-1294. doi: 10.1038/jid.2013.540. Epub 2013 Dec 23.

A quantitative increase in regulatory T cells controls development of vitiligo.

Author information

1
Department of Surgery, Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
2
Department of Pathology, Microbiology and Immunology, Oncology Research Institute, Loyola University, Maywood, Illinois, USA.
3
Department of Surgery, Loyola University, Maywood, Illinois, USA.
4
Department of Surgery, Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA. Electronic address: mehrotr@musc.edu.

Abstract

T-cell cytolytic activity targeting epidermal melanocytes is shown to cause progressive depigmentation and autoimmune vitiligo. By using the recently developed transgenic mice h3TA2 that carry T cells with a HLA-A2-restricted human tyrosinase peptide (h-Tyr)-reactive TCR and develop spontaneous vitiligo from an early age, we addressed the mechanism regulating autoimmune vitiligo. Depigmentation was significantly impaired only in IFN-γ-knockout h3TA2 mice but not in TNF-α- or perforin-knockout h3TA2 mouse strains, confirming a central role for IFN-γ in vitiligo development. In addition, regulatory T cells (Tregs) were relatively abundant in h3TA2-IFN-γ(-/-) mice, and depletion of the Treg-engaging anti-CD25 antibody fully restored the depigmentation phenotype in h3TA2-IFN-γ(-/-) mice, mediated in part through the upregulation of proinflammatory cytokines such as IL-17 and IL-22. Further therapeutic potential of Treg abundance in preventing progressive depigmentation was evaluated by adoptively transferring purified Treg or using rapamycin. Both the adoptive transfer of Tregs and the use of rapamycin induced a lasting remission of vitiligo in mice treated at the onset of disease, or in mice with established disease. This leads us to conclude that reduced regulatory responses are pivotal to the development of vitiligo in disease-prone mice, and that a quantitative increase in the Treg population may be therapeutic for vitiligo patients with active disease.

PMID:
24366614
PMCID:
PMC3989443
DOI:
10.1038/jid.2013.540
[Indexed for MEDLINE]
Free PMC Article

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