title: T regulatory cells in atopic dermatitis and subversion of their activity by superantigens.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a chronic inflammatory skin disease involving colonization by superantigen (SAg)-secreting Staphylococcus aureus. CD4+CD25+ T regulatory (Treg) cells are thought to play an important role in controlling inflammatory responses.
  
  
  OBJECTIVE
  In this study we examined whether Treg cells might be deficient in patients with AD.
  
  
  METHODS
  CD4+CD25+ and CD4+CD25- T cells were isolated from PBMCs by using immunomagnetic beads. Cells were cultured with anti-CD3 or SAg, staphylococcal enterotoxin B (SEB), for 72 hours. Proliferation was measured by means of tritiated thymidine incorporation. CD4, CD8, CD25, and cutaneous lymphocyte-associated antigen expression on PBMCs was assessed by means of flow cytometry. RNA was extracted from isolated subsets of T cells, and the results of real-time PCR for FoxP3 mRNA were determined.
  
  
  RESULTS
  Surprisingly, CD4+CD25+ T cells were significantly (P <.01) increased in patients with AD (6.68%+/-0.99%, n=15) compared with in asthmatic patients (3.42%+/-0.58%, n=12) or nonatopic healthy control subjects (3.34%+/-0.43%, n=14). Patients with AD also had a higher expression of CD25+ in skin-homing, CD4+, cutaneous lymphocyte-associated antigen-positive T cells than asthmatic and nonatopic subjects, with values of 35.95% versus 22.44% versus 23.03%, respectively (P <.006). Only CD4+CD25+ cells expressed FoxP3, whereas CD4+CD25- T cells and CD4- cells did not. Consistent with known properties of Treg cells, CD4+CD25+ cells were anergic to anti-CD3 stimulation. When CD4+CD25+ cells from each study group were mixed with CD4+CD25- cells, proliferative responses were equally suppressed after anti-CD3 stimulation. In contrast, after SEB stimulation, CD4+CD25+ cells were no longer anergic. Furthermore, when CD4+CD25+ cells were mixed with CD4+CD25- cells and stimulated with SEB, the suppressive function of Treg cells was reversed.
  
  
  CONCLUSIONS
  Patients with AD have significantly increased numbers of peripheral blood Treg cells with normal immunosuppressive activity. However, after SAg stimulation, Treg cells lose their immunosuppressive activity. These data suggest a novel mechanism by which SAgs could augment T-cell activation in patients with AD.
authors.affiliation: Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Liang-Shiou
authors.initials: LS
authors.lastname: Ou
authors.forename: Elena
authors.initials: E
authors.lastname: Goleva
authors.forename: Clifton
authors.initials: C
authors.lastname: Hall
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D016022:Case-Control Studies; D002455:Cell Division; D002469:Cell Separation; D017635:Clonal Anergy / Q000187:drug effects; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology*; D004768:Enterotoxins / Q000494:pharmacology*; D051858:Forkhead Transcription Factors; D006801:Humans; D018655:Lymphocyte Count; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D004768:Enterotoxins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2; D018089:Superantigens; C031818:enterotoxin B, staphylococcal