Cosmi Lorenzo, Liotta Francesco, Angeli Roberta, Mazzinghi Benedetta, Santarlasci Veronica, Manetti Roberto, Lasagni Laura, Vanini Vittorio, Romagnani Paola, Maggi Enrico, Annunziato Francesco, Romagnani Sergio
Department of Internal Medicine, University of Florence, Florence, Italy.
Blood. 2004 Apr 15;103(8):3117-21. doi: 10.1182/blood-2003-09-3302. Epub 2003 Dec 24.
T-cell clones generated from both CD4+CD25+ and CD8+CD25+ human thymocytes were assessed for their ability to suppress the proliferative response to allogeneic stimulation of type 1 T-helper (Th1) or type 2 T-helper (Th2) clones derived from autologous CD4+CD25- thymocytes. Both CD4+ and CD8+ T-regulatory (Treg) cells completely suppressed the proliferation of Th1 clones but exhibited significantly lower suppressive activity on the proliferation of Th2 clones. The partial suppressive effect on Th2 cells was further reduced by the addition in culture of interleukin-4 (IL-4), whereas it was increased in the presence of an anti-IL-4 monoclonal antibody (mAb). The suppressive activity on Th2 clones was also completely inhibited by the addition of IL-7, IL-9, and IL-15 but not of IL-2, whereas the suppressive effect on Th1 clones was only reverted by the addition of IL-15. Of note, Th2 clones expressed significantly higher amounts of mRNA for IL-4 receptor (IL-4R) and IL-9R alpha chains than Th1 clones, whereas the expression of mRNA for IL-2R, IL-7R, and IL-15R alpha chains was comparable. Taken together, these findings demonstrate that Th2 cells have a lower susceptibility than Th1 cells to the suppressive activity of human CD25+ regulatory thymocytes, because they are able to produce, and to respond to, growth factors distinct from IL-2, such as IL-4 and IL-9.
对从CD4+CD25+和CD8+CD25+人胸腺细胞产生的T细胞克隆进行评估，以检测其抑制源自自体CD4+CD25-胸腺细胞的1型辅助性T细胞（Th1）或2型辅助性T细胞（Th2）克隆对同种异体刺激的增殖反应的能力。CD4+和CD8+调节性T细胞（Treg）均完全抑制Th1克隆的增殖，但对Th2克隆增殖的抑制活性明显较低。在培养物中添加白细胞介素-4（IL-4）后，对Th2细胞的部分抑制作用进一步降低，而在存在抗IL-4单克隆抗体（mAb）的情况下，该抑制作用增强。添加IL-7、IL-9和IL-15可完全抑制对Th2克隆的抑制活性，但添加IL-2则不能，而添加IL-15仅能逆转对Th1克隆的抑制作用。值得注意的是，Th2克隆表达的IL-4受体（IL-4R）和IL-9Rα链的mRNA量明显高于Th1克隆，而IL-2R、IL-7R和IL-15Rα链的mRNA表达相当。综上所述，这些发现表明，Th2细胞比Th1细胞对人CD25+调节性胸腺细胞的抑制活性敏感性更低，因为它们能够产生并对不同于IL-2的生长因子（如IL-4和IL-9）作出反应。
