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.


CONCLUSIONS
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.


CONCLUSIONS
Caution should be advised in interpreting allergic disorders as simply resulting from defective Treg cell activity.
Maggi
Laura
L
Excellence Center for Research, Transfer, and High Education DENOthe, University of Florence, Italy.
Santarlasci
Veronica
V
Liotta
Francesco
F
Frosali
Francesca
F
Angeli
Roberta
R
Cosmi
Lorenzo
L
Maggi
Enrico
E
Romagnani
Sergio
S
Annunziato
Francesco
F
D000941:Antigens / Q000378:metabolism; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D003546:Cysteine Endopeptidases; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology; D000939:Epitopes; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood* / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D009994:Osmolar Concentration; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
D000941:Antigens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D000939:Epitopes; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1