T regulatory cells in atopic dermatitis and subversion of their activity by superantigens - PubMed (original) (raw)
T regulatory cells in atopic dermatitis and subversion of their activity by superantigens
Liang-Shiou Ou et al. J Allergy Clin Immunol. 2004 Apr.
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.
Conclusion: 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.
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