Demonstration of circulating allergen-specific CD4(+)CD25(high)Foxp3(+) T-regulatory cells in both nonatopic and atopic individuals.

Abstract Background: CD4CD25Foxp3 T-regulatory (Treg) cells play a fundamental role in the control of autoimmunity. Whether human CD4CD25Foxp3 Treg cells that recognize foreign antigens also exist is less clear. Objective: To investigate the existence in humans of circulating Treg cells able to recognize exogenous antigens, including allergens. Methods: CD4CD25highFoxp3 and CD4CD25-Foxp3- cells were purified from human peripheral blood and cultured for 15 days with autologous dendritic cells (DCs), unloaded, or loaded with Der p 1 allergen or the bacterial antigen streptokinase (SK). Results: CD4CD25highFoxp3 circulating T cells obtained from healthy nonatopic subjects and cultured with Der p 1–loaded DCs, but not those cultured with either unloaded or SK-loaded DCs, suppressed the proliferative response to Der p 1 of autologous Der p 1–specific T cells generated from the CD4CD25-Foxp3- subset. The antigen specificity of either Der p 1–CD4CD25highFoxp3 or SK CD4CD25highFoxp3 T cells was confirmed even at clonal level. Finally, under the same experimental conditions, functionally active Der p 1–specific Treg cells were obtained from the pool of circulating CD4CD25highFoxp3 T cells of Der p 1–sensitive, atopic individuals. Conclusion: These data provide undoubted demonstration of the existence of human CD4CD25highFoxp3 circulating Treg cells specific for exogenous antigens, including the Der p 1 allergen, and indicate that CD4CD25highFoxp3 Treg cells specific for Der p 1 are present and functionally active in both nonatopic and Der p 1–sensitive, atopic individuals. Clinical implications: Caution should be advised in interpreting allergic disorders as simply resulting from defective Treg cell activity. (J Allergy Clin Immunol 2007;120:429-36.)