Decreased regulatory T‐cells and CD4⁺/CD8⁺ ratio correlate with disease onset and progression in patients with generalized vitiligo

Abstract

The aim of present study was to evaluate CD4(+) /CD8(+) ratio and CD4(+) CD25(hi) FoxP3(+) Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4(+) /CD8(+) ratio and Tregs in 82 patients and 50 controls. CD8(+) T-cell counts were significantly higher in GV patients as compared with controls (p = 0.003). Active GV patients showed higher CD8(+) T-cell counts compared with stable GV patients (p = 0.001). The CD4(+) /CD8(+) ratio decreased significantly in patients as compared with controls (p = 0.001). Moreover, the ratio in active GV patients significantly lowered as compared with stable GV patients (p = 0.002). Significant decrease in Treg cell percentage and counts in GV patients was observed compared with controls (p = 0.009, p = 0.008) with significant reduction in FoxP3 expression (p = 0.024). Treg cell percentage and counts were significantly decreased in active GV patients compared with stable GV patients (p = 0.007, p = 0.002). Our results suggest that an imbalance of CD4(+) /CD8(+) ratio and natural Tregs in frequency and function might be involved in the T-cell mediated pathogenesis of GV and its progression.

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

“…Such alterations might lead to the higher levels and activation of cytotoxic T cells (Fig. 1) which have been reported in individuals with the disease [10,11]. Currently, however, studies examining any reciprocal relationship between CD4 + CD25 + FoxP3 + Tregs and CD8 + in vitiligo progression are lacking.…”

“…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].…”

“…1). 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].…”