Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo

Abstract

Summary Auto‐reactive cytotoxic T lymphocytes play a key role in the progressive loss or destruction of melanocytes in vitiligo but the mechanism underlying the loss of self‐tolerance is unknown. A deregulation of regulatory T‐cell biology has recently been suggested. The analysis of the suppressive effects of peripheral T regulatory cells in vitiligo patients revealed a functional defect in seven of 15 cases. This defect was strongly correlated with disease activity. The evaluation of the percentage of peripheral regulatory T lymphocytes did not reveal any intrinsic quantitative defect. Yet, a decrease in the percentage of such cells was noted in patients with progressive forms, suggesting a recruitment of regulatory T cells from the peripheral blood to the site of injury. This was further corroborated by the significant increase of Forkhead box P3 expression in the vitiliginous skin of patients. Our data support the involvement of a functional defect of peripheral regulatory T cells in the pathogenesis of vitiligo and open new possibilities to advance therapeutic approaches.

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

“…More recently, repigmentation in a mouse model of spontaneous epidermal depigmentation was found to be accompanied by an increased Treg cell infiltration, suggesting their importance in preventing an ongoing immune response against melanocytes [17]. To date, several studies have indicated perturbations in Treg cell numbers and/or function in vitiligo patients [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Such alterations might lead to the higher levels and activation of cytotoxic T cells (Fig.…”

“…Several studies have been carried out to look for alterations in Treg cell numbers in vitiligo (Table 1) [10][11][12][13][14][15][16][17][18][19][20][21][22][23]26,27]. Assessment of circulating Tregs by flow cytometric analysis has revealed a decrease in their numbers in vitiligo patients compared to controls [10,11,13].…”

“…Assessment of circulating Tregs by flow cytometric analysis has revealed a decrease in their numbers in vitiligo patients compared to controls [10,11,13].…”

“…Significant reductions in the function of peripheral Tregs have been demonstrated in progressive vitiligo using assays which measure how well these cells can inhibit the proliferation of and cytokine production from stimulated autologous CD8 + T cells (Table 1) [10,13]. The possible causes of Treg cell functional defects in vitiligo have been investigated and these are summarised below.…”

“…In addition, there is a global expansion and widespread activation of the CD8 + T cell population in vitiligo patients [10][11][12]. So far, however, the exact mechanisms underlying the induction and activation of autoreactive CD8 + T cells and the loss of tolerance to melanocyte autoantigens in vitiligo are not clear, but as with other autoimmune disorders, it seems likely that this loss of tolerance to self must involve some defect in regulatory T cell (Tregs) function [10,11,13].…”