Overexpression of TGF-β or Foxp3 in T Cells on Their Regulatory Function

• Main Authors: Han-Fang Cheng, 鄭涵方
• Other Authors: Bor-Luen Chiang
• Format: Others
• Language: en_US
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/65934050232724402573

碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 94 === The immune system has evolved the mechanisms to recognize and eliminate threats, as well as to avoid deleterious responses such as self-destruction and inflammation. Such unresponsiveness to self-antigens and nonpathogenic environmental antigens is called immune tolerance. Regulatory T cells (Tregs) have been demonstrated to play a critical role in maintaining immune tolerance and homeostasis by actively suppressing the development of autoimmune and allergic responses. It has already been reported that the forkhead family transcription factor Foxp3 is critically important for the development and function of the regulatory T cells. It is expressed in CD4+ CD25+, but not CD4+ CD25- T cells and acts as a silencer of cytokine gene promoters in CD4+ CD25+ Treg cells. In addition, studies have shown that the cytokine TGF-β produced by Tregs potently suppresses immune responses. Nonetheless, little is known about the correlation between Foxp3 and TGF-β. In this study, we investigated the effect of overexpression of TGF-β through lentiviral system upon IL-2 secretion and Foxp3 expression in human leukemia cells. Likewise, we investigated the effect of Foxp3 overexpression on the protein level of TGF-β and the components of TGF-β-mediated signaling cascade, such as Smad2 and Smad3. Finally, we examined the effect of Foxp3 on TGF-β1 signaling. We addressed that TGF-β overexpression suppresses stimulation-induce IL-2 hypersecretion and induces Foxp3 expression. Overexpression of Foxp3 had little influence on TGF-βsecretion while significantly enhanced surface-bound TGF-β TGF-βRII and Smad3. Furthermore, we described that Foxp3-overexpressed T cells were more susceptible to TGF-β1-induced phosphorylation of Smad2. These findings help to elucidate the molecular mechanisms of development and action of regulatory T cells.