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.
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.
Authors: Creg J Workman; Andrea L Szymczak-Workman; Lauren W Collison; Meenu R Pillai; Dario A A Vignali Journal: Cell Mol Life Sci Date: 2009-04-24 Impact factor: 9.261
Authors: R Knobler; G Berlin; P Calzavara-Pinton; H Greinix; P Jaksch; L Laroche; J Ludvigsson; P Quaglino; W Reinisch; J Scarisbrick; T Schwarz; P Wolf; P Arenberger; C Assaf; M Bagot; M Barr; A Bohbot; L Bruckner-Tuderman; B Dreno; A Enk; L French; R Gniadecki; H Gollnick; M Hertl; C Jantschitsch; A Jung; U Just; C-D Klemke; U Lippert; T Luger; E Papadavid; H Pehamberger; A Ranki; R Stadler; W Sterry; I H Wolf; M Worm; J Zic; C C Zouboulis; U Hillen Journal: J Eur Acad Dermatol Venereol Date: 2014-01 Impact factor: 6.166
Authors: J L Hayworth; K J Kasper; M Leon-Ponte; C A Herfst; D Yue; W C Brintnell; D M Mazzuca; D E Heinrichs; E Cairns; J Madrenas; D W Hoskin; J K McCormick; S M M Haeryfar Journal: Clin Exp Immunol Date: 2009-07 Impact factor: 4.330