A quantitative increase in regulatory T cells controls development of vitiligo Journal Article

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Authors: Chatterjee, S; Eby, J. M.; Al-Khami, A. A.; Soloshchenko, M.; Kang, H. K.; Kaur, N.; Naga, O. S.; Murali, A.; Nishimura, M. I.; Le Poole, I. C.; Mehrotra, S
Article Title: A quantitative increase in regulatory T cells controls development of vitiligo
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-gamma-knockout h3TA2 mice but not in TNF-alpha- or perforin-knockout h3TA2 mouse strains, confirming a central role for IFN-gamma in vitiligo development. In addition, regulatory T cells (Tregs) were relatively abundant in h3TA2-IFN-gamma(-/-) mice, and depletion of the Treg-engaging anti-CD25 antibody fully restored the depigmentation phenotype in h3TA2-IFN-gamma(-/-) 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.
Journal Title: The Journal of investigative dermatology
Volume: 134
Issue: 5
ISSN: 1523-1747; 0022-202X
Publisher: Unknown  
Journal Place: United States
Date Published: 2014
Start Page: 1285
End Page: 1294
Language: eng
DOI/URL:

10.1038/jid.2013.540
Notes: LR: 20150127; GR: P01 CA154778/CA/NCI NIH HHS/United States; GR: P01 CA154778/CA/NCI NIH HHS/United States; GR: P30 CA138313/CA/NCI NIH HHS/United States; GR: P30 CA138313/CA/NCI NIH HHS/United States; GR: R01 AR057643/AR/NIAMS NIH HHS/United States; GR: R01 AR057643/AR/NIAMS NIH HHS/United States; GR: R01 CA138930/CA/NCI NIH HHS/United States; GR: R01CA138930/CA/NCI NIH HHS/United States; GR: R21 AR056524/AR/NIAMS NIH HHS/United States; GR: R21 AR056524/AR/NIAMS NIH HHS/United States; JID: 0426720; 0 (Cxcr3 protein, mouse); 0 (Immunosuppressive Agents); 0 (Receptors, CCR5); 0 (Receptors, CXCR3); 0 (Tumor Necrosis Factor-alpha); 82115-62-6 (Interferon-gamma); W36ZG6FT64 (Sirolimus); NIHMS549279; OID: NLM: NIHMS549279; OID: NLM: PMC3989443; 2013/08/18 [received]; 2013/11/11 [revised]; 2013/11/14 [accepted]; 2013/12/23 [aheadofprint]; ppublish