ABSTRACT
PURPOSE: Cutaneous lymphocyte-associated antigen (CLA)-expressing CD8âºT 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 CD8âºCLAâºT cells might be underlying mechanism in AD. MATERIALS AND METHODS: CD8âºCLAâºT cells and Tregs were obtained from the peripheral blood of AD patients and control volunteers. The frequencies of CD8âºCLAâºT cells were evaluated. The proliferative responses of CD8âºCLAâºT cells were assessed by flow cytometry, and the levels of transforming growth factor-ß1 (TGF-ß1) 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 CD8âºCLAâºT cells in AD, and lower inhibitory ability of Tregs on proliferation of CD8âºCLAâºT cells in AD. Meanwhile, the levels of TGF-ß1 produced by Tregs were significantly lower in AD, and anti-TGF-ß1 abolished such suppression. CONCLUSION: The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8âºCLAâºT cells, mediated by TGF-ß1, plays an important role in the pathogenesis of AD.
