A Quantitative Increase in Regulatory T Cells Controls Development of Vitiligo

Abstract

T cell cytolytic activity targeting epidermal melanocyte is shown to cause progressive depigmentation and autoimmune vitiligo. Using the recently developed transgenic mice h3TA2 that carry T cell with a HLA-A2 restricted human tyrosinase 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. Additionally, the regulatory T cells (Treg) were relatively abundant in h3TA2-IFN-γ−/− mice, and depletion of Treg employing anti-CD25 antibody fully restored the depigmentation phenotype in h3TA2-IFN-γ−/− mice mediated in part through upregulation of pro-inflammatory cytokines as IL-17and IL-22. Further therapeutic potential of Treg abundance in preventing progressive depigmentation was evaluated by adoptively transferring purified Treg or using rapamycin. Both adoptive transfer of Treg and rapamycin induced 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.

Reducing CD73 Expression by IL1β-Programmed Th17 Cells Improves Immunotherapeutic Control of Tumors

“…Detailed protocols for staining the cells for surface markers and intracellular cytokines have been described earlier (15), and in supplementary methods. Detailed methodology for q-PCR is provided in supplementary method section.…”

The role of IL-17 in vitiligo: A review

“…This trend was also seen after antigen-specific TCR stimulation with cognate peptide (p<0.01). Additionally, there were increased numbers of IL-17+ T cells seen infiltrating the skin of these mice (p<0.01)[68]. …”

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

“…Recently, Chatterjee et al [81] have reported the first animal study proposing Tregs as a therapeutic for vitiligo. Using transgenic mice that carry T cells with a human leukocyte antigen (HLA)-A2-restricted human tyrosinase peptide-reactive T cell receptor and that develop spontaneous vitiligo from an early age, adoptively transferred Tregs were found to induce a lasting remission of vitiligo in mice treated at the onset of disease, or in mice with established disease.…”