title: Attenuation of peripheral regulatory T-cell suppression of skin-homing CD8⁺T cells in atopic dermatitis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Yidu Central Hospital, Weifang Medical University, Weifang, P.R. China.
authors.forename: Bao-Xiang
authors.initials: BX
authors.lastname: Zhang
authors.affiliation: Department of Health Statistics, Public Health College of Weifang Medical University, Weifang, P.R. China.
authors.forename: Jun-Cheng
authors.initials: JC
authors.lastname: Lyu
authors.affiliation: Department of Clinical Laboratory, Yidu Central Hospital, Weifang Medical University, Weifang, P.R. China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Yidu Central Hospital, Weifang Medical University, Weifang, P.R. China.
authors.forename: Dian-Qin
authors.initials: DQ
authors.lastname: Feng
authors.affiliation: Department of Dermatology, Yidu Central Hospital, Weifang Medical University, Weifang, P.R. China.
authors.forename: Dian-Cai
authors.initials: DC
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Weifang Skin Disease Hospital, Weifang, P.R. China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Bi
authors.affiliation: Department of Dermatology, Yidu Central Hospital, Weifang Medical University, Weifang, P.R. China.
authors.forename: Zhi-Wu
authors.initials: ZW
authors.lastname: Duan
authors.affiliation: Department of Stomatology, Yidu Central Hospital, Weifang Medical University, Weifang, P.R. China. dentistdg@sina.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Ding
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002469:Cell Separation; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D054353:Perforin / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D053773:Transforming Growth Factor beta1; D054353:Perforin; D016753:Interleukin-10; D053804:Granzymes
keywords: CD8⁺T cell; Cutaneous lymphocyte-associated antigen; T cells; atopic dermatitis; regulatory