Attenuation of Peripheral Regulatory T-Cell Suppression of Skin-Homing CD8+T Cells in Atopic Dermatitis.
10.3349/ymj.2015.56.1.196
- Author:
Bao Xiang ZHANG
1
;
Jun Cheng LYU
;
Hai Bo LIU
;
Dian Qin FENG
;
Dian Cai ZHANG
;
Xing Jie BI
;
Zhi Wu DUAN
;
Gang DING
Author Information
1. Department of Dermatology, Yidu Central Hospital, Weifang Medical University, Weifang, P.R. China.
- Publication Type:Original Article
- Keywords:
Cutaneous lymphocyte-associated antigen;
CD8+T cell;
regulatory;
T cells;
atopic dermatitis
- MeSH:
Adult;
Aged;
CD8-Positive T-Lymphocytes/drug effects/*immunology;
Case-Control Studies;
Cell Proliferation;
Cell Separation;
Dermatitis, Atopic/*immunology/pathology;
Female;
Granzymes/metabolism;
Humans;
Interleukin-10/metabolism;
Lymphocyte Count;
Male;
Perforin/metabolism;
Skin/*immunology/pathology;
T-Lymphocytes, Cytotoxic/drug effects/immunology;
T-Lymphocytes, Regulatory/drug effects/*immunology;
Transforming Growth Factor beta1/pharmacology
- From:Yonsei Medical Journal
2015;56(1):196-203
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-beta1 (TGF-beta1) 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-beta1 produced by Tregs were significantly lower in AD, and anti-TGF-beta1 abolished such suppression. CONCLUSION: The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8+CLA+T cells, mediated by TGF-beta1, plays an important role in the pathogenesis of AD.
