- 作者: Ken Matsui Satoshi Jodo Sheng Xiao Shyr-Te Ju
- 作者服務機構: Arthritis Center, Department of Medicine, Boston University School of Medicine, Boston, mass., USA
- 中文摘要: --
- 英文摘要: Studies of several gene knockout mice suggest an inter-esting association of a moderate T cell response withsystemic autoimmune diseases. In addition, CD95 ligand(FasL) expression in some strains of these mice is im-paired. Because FasL is critically involved in regulatingperipheral tolerance, there may be a link between au-toimmune diseases and a moderate T cell response thatcannot activate the FasL gene. Here, we propose thatthere are two thresholds of T cell activation. When mod-erately stimulated, T cells can be activated to the low(1st) threshold, which permits the induction of CD40L,IL-2, IL-4, and other components that help the immuneresponse. The high (2nd) activation threshold can onlybe achieved by a strong and concurrent stimulationthrough TCR and IL-2R. Once the high threshold isreached, FasL is produced to induce apoptosis of theactivated T and B cells. In the absence of the FasL-mediated downregulation,the activated B cells becomeefficient antigen-presenting cells for self-antigens andexcellent responders for T cell help. Such an exacerbat-ing condition, induced by recurrent and moderate activa-tion, favors the development of autoreactive T cells andautoantibody production. Evidence supporting this hy-pothesis and some predictions that can be tested aredescribed.
- 中文關鍵字: --
- 英文關鍵字: autoimmunity. Apoptosis, IL-2. FasL. Tolerance