Attenuation of Peripheral Regulatory T-Cell Suppression of Skin-Homing CD8(+)T Cells in Atopic Dermatitis

作者：Zhang Bao Xiang; Lyu Jun Cheng; Liu Hai Bo; Feng Dian Qin; Zhang Dian Cai; Bi Xing Jie; Duan Zhi Wu; Ding Gang^*

来源：Yonsei Medical Journal, 2015, 56(1): 196-203.

DOI：10.3349/ymj.2015.56.1.196

• Cutaneous lymphocyte-associated antigen
• CD8(+)T cell
• regulatory
• T cells
• atopic dermatitis

Purpose: Cutaneous lymphocyte-associated antigen (CLA)-expressing CD8(+)T cells have been known to play an important role in the pathogenesis of atopic dermatitis (AD). However, the mechanisms underlying the loss of self-tolerance remain unclear. Regulatory T cells (Tregs) play a key role in the development of homeostasis in the immune system. We, therefore, hypothesized that a reduced ability of Tregs to inhibit autologous CD8(+)CLA(+)T cells might be underlying mechanism in AD. Materials and Methods: CD8(+)CLA(+)T cells and Tregs were obtained from the peripheral blood of AD patients and control volunteers. The frequencies of CD8(+)CLA(+)T cells were evaluated. The proliferative responses of CD8(+)CLA(+)T cells were assessed by flow cytometry, and the levels of transforming growth factor-beta 1 (TGF-beta 1) and interleukin-10 (IL-10) in culture supernatants were detected by enzyme-linked immunosorbent assay. Results: Our results revealed higher frequency and increased expression of perforin and granzyme-B in peripheral CD8(+)CLA(+)T cells in AD, and lower inhibitory ability of Tregs on proliferation of CD8(+)CLA(+)T cells in AD. Meanwhile, the levels of TGF-beta 1 produced by Tregs were significantly lower in AD, and anti-TGF-beta 1 abolished such suppression. Conclusion: The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8(+)CLA(+)T cells, mediated by TGF-beta 1, plays an important role in the pathogenesis of AD.

• 出版日期2015-1-1
• 单位潍坊医学院