Attenuation of Peripheral Regulatory T-Cell Suppression of Skin-Homing CD8(+)T Cells in 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-β1 (TGF-β1) 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-β1 produced by Tregs were significantly lower in AD, and anti-TGF-β1 abolished such suppression. CONCLUSION: The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8(+)CLA(+)T cells, mediated by TGF-β1, plays an important role in the pathogenesis of AD.