Maggi Laura, Santarlasci Veronica, Liotta Francesco, Frosali Francesca, Angeli Roberta, Cosmi Lorenzo, Maggi Enrico, Romagnani Sergio, Annunziato Francesco
Excellence Center for Research, Transfer, and High Education DENOthe, University of Florence, Italy.
J Allergy Clin Immunol. 2007 Aug;120(2):429-36. doi: 10.1016/j.jaci.2007.05.002. Epub 2007 Jul 2.
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.
To investigate the existence in humans of circulating Treg cells able to recognize exogenous antigens, including allergens.
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).
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.
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.
Caution should be advised in interpreting allergic disorders as simply resulting from defective Treg cell activity.
CD4(+)CD25(+)Foxp3(+)调节性T（Treg）细胞在自身免疫控制中发挥着重要作用。人类中是否也存在识别外来抗原的CD4(+)CD25(+)Foxp3(+) Treg细胞尚不清楚。
研究人类中能够识别包括过敏原在内的外源性抗原的循环Treg细胞的存在情况。
从人外周血中纯化CD4(+)CD25(高)Foxp3(+)和CD4(+)CD25(-)Foxp3(-)细胞，并用自体树突状细胞（DCs）、未负载或负载了Der p 1过敏原或细菌抗原链激酶（SK）的DCs培养15天。
从健康非特应性受试者获得的CD4(+)CD25(高)Foxp3(+)循环T细胞，与负载了Der p 1的DCs共同培养后，而非与未负载或负载了SK的DCs共同培养后，抑制了从CD4(+)CD25(-)Foxp3(-)亚群产生的自体Der p 1特异性T细胞对Der p 1的增殖反应。即使在克隆水平，Der p 1-CD4(+)CD25(高)Foxp3(+)或SK-CD4(+)CD25(高)Foxp3(+) T细胞的抗原特异性也得到了证实。最后，在相同实验条件下，从Der p 1敏感的特应性个体的循环CD4(+)CD25(高)Foxp3(+) T细胞池中获得了功能活跃的Der p 1特异性Treg细胞。
这些数据无疑证明了人类中存在针对外源性抗原（包括Der p 1过敏原）的CD4(+)CD25(高)Foxp3(+)循环Treg细胞，并表明针对Der p 1的CD4(+)CD25(高)Foxp3(+) Treg细胞在非特应性个体和Der p 1敏感的特应性个体中均存在且功能活跃。
在将过敏性疾病简单地解释为仅由Treg细胞活性缺陷导致时应谨慎。
