Mao Lin1, Bao-Xiang Zhang2, Nan Shen2, Xue-Jiao Dong2, Ci Zhang2, Xiao-Yi Qi3, Jie Zhu4, Yu-Zhong Li4, Mao-Qiang Man5, Cai-Xia Tu1. 1. Department of Dermatology,, College of Integrative Medicine. 2. Department of Dermatology. 3. Department of Dermatology,, College of Integrative Medicine,, Department of Clinical Laboratory, 2nd Affiliated Hospital of Dalian Medical University, No.467 Zhongshan Road, 116027 Dalian, Liaoning Province, P. R. China, Department of Dermatology, Northern California Institute for Research and Education, San Francisco CA 94121, USA. 4. Department of Clinical Laboratory, 2nd Affiliated Hospital of Dalian Medical University, No.467 Zhongshan Road, 116027 Dalian, Liaoning Province, P. R. China. 5. Department of Dermatology, Northern California Institute for Research and Education, San Francisco CA 94121, USA.
Abstract
BACKGROUND: Recent studies have shown that vitiligo is a T-cell mediated autoimmune disease. Skin-homing cytotoxic T lymphocytes expressing cutaneous lymphocyte-associated antigen (CLA) have been suggested to be responsible for the destruction of melanocytes in vitiligo. An aberration in the suppressive function of regulatory T cells (Tregs) has been reported in vitiligo patients. However, whether the weakened suppressive ability of the Tregs contributes to hyper-activated skin homing CD8(+)CLA(+) T cells remains to be determined. OBJECTIVES: To investigate the inhibition of circulating Tregs on the proliferation of autologous CD8(+)CLA(+) T cells in non-segmental vitiligo patients. METHODS: CD8(+)CLA(+) T cells and Tregs were obtained from the peripheral blood of 13 non-segmental vitiligo patients and 7 controls. The proliferative responses of CD8(+)CLA(+) T cells were assessed in the absence or presence of autologous Tregs, and the levels of Transforming Growth Factor β1(TGF-β1) and IL-10 in culture supernatants were detected by enzyme-linked immunosorbent assay. RESULTS: The proliferative responses of circulating CD8(+)CLA(+) T cells in the presence of Tregs were significantly higher in the active vitiligo than in the stable vitiligo and control groups. Tregs from active vitiligo patients exhibited a lower inhibitory effect on proliferation of CD8(+)CLA(+) T cells. The levels of TGF-β1 produced by Tregs were significantly lower in active vitiligo than other groups and anti-TGF-β1 antibodies could abrogate the suppressive function of Tregs. CONCLUSIONS: The functional activity of Tregs is compromised in active vitiligo patients. TGF-β1 plays an important role in the autoimmune mechanism of the disease.
BACKGROUND: Recent studies have shown that vitiligo is a T-cell mediated autoimmune disease. Skin-homing cytotoxic T lymphocytes expressing cutaneous lymphocyte-associated antigen (CLA) have been suggested to be responsible for the destruction of melanocytes in vitiligo. An aberration in the suppressive function of regulatory T cells (Tregs) has been reported in vitiligo patients. However, whether the weakened suppressive ability of the Tregs contributes to hyper-activated skin homing CD8(+)CLA(+) T cells remains to be determined. OBJECTIVES: To investigate the inhibition of circulating Tregs on the proliferation of autologous CD8(+)CLA(+) T cells in non-segmental vitiligo patients. METHODS:CD8(+)CLA(+) T cells and Tregs were obtained from the peripheral blood of 13 non-segmental vitiligo patients and 7 controls. The proliferative responses of CD8(+)CLA(+) T cells were assessed in the absence or presence of autologous Tregs, and the levels of Transforming Growth Factor β1(TGF-β1) and IL-10 in culture supernatants were detected by enzyme-linked immunosorbent assay. RESULTS: The proliferative responses of circulating CD8(+)CLA(+) T cells in the presence of Tregs were significantly higher in the active vitiligo than in the stable vitiligo and control groups. Tregs from active vitiligo patients exhibited a lower inhibitory effect on proliferation of CD8(+)CLA(+) T cells. The levels of TGF-β1 produced by Tregs were significantly lower in active vitiligo than other groups and anti-TGF-β1 antibodies could abrogate the suppressive function of Tregs. CONCLUSIONS: The functional activity of Tregs is compromised in active vitiligo patients. TGF-β1 plays an important role in the autoimmune mechanism of the disease.
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Keywords:
CD8+ T cell; cutaneous lymphocyte-associated antigen; regulatory T cells; vitiligo