Demonstration of circulating allergen-specific CD4+CD25highFoxp3+ T-regulatory cells in both nonatopic and atopic individuals

Background CD4 + CD25 + Foxp3 + T-regulatory (Treg) cells play a fundamental role in the control of autoimmunity. Whether human CD4 + CD25 + Foxp3 + 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 CD4 + CD25 high Foxp3 + and CD4 + CD25 - 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 CD4 + CD25 high Foxp3 + 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 CD4 + CD25 - Foxp3 - subset. The antigen specificity of either Der p 1–CD4 + CD25 high Foxp3 + or SK–CD4 + CD25 high Foxp3 + 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 CD4 + CD25 high Foxp3 + T cells of Der p 1–sensitive, atopic individuals. Conclusion These data provide undoubted demonstration of the existence of human CD4 + CD25 high Foxp3 + circulating Treg cells specific for exogenous antigens, including the Der p 1 allergen, and indicate that CD4 + CD25 high Foxp3 + 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.