The mechanism of activation-induced T cell death

• Main Authors: Huang, Yu Wen, 黃育文
• Other Authors: Lin, Rong Hua
• Format: Others
• Language: zh-TW
• Published: 1996
• Online Access: http://ndltd.ncl.edu.tw/handle/54034845703700676889

碩士 === 國立臺灣大學 === 免疫學研究所 === 84 === The activation of T cellsrequirs two signals. The first is delivered form the TCR/CD3 complx and the second signal is tri- ggered by accessory molecules on APC.The CD28 signaling is the most potent costimulatory pathway identified to date. However, ligation of the TCR complex on previously activated T cells and T cell line has been shown to result in activation-induced cell death (AICD) through apoptosis. This mechanism of homeostasis maintains the numbers and function of T cells. AICD is belived to play a centrol role in the homeostatic regulation of immune response. It is suggested that Fas and Fas ligand interaction play an important role in inducing AICD.How- ever,AICD can also be induced in peripheral T cell of lpr/lpr mice. In addition to Fas and FasL,other molecules may also exist to participate the deletion of activated T in peripheral system. Furthermore,not all previously activated T cells undergo apopto- sis after activation.So,the mechanism controlling the differen- tial susceptibility of T cells to AICD is still not clear. Cross-linking of CD28 has no effect on bcl-2 gene expression,but can augment the expression of bcl-xL gene.Therefore we have investigated whether CD28 costimulation can prevent T cell AICD. We identify,herein,a novel function of murine CD28 in the regulation of activation-induced cell death by in vitro cell culture system.Our data shown that addition of anti-CD28mAb can prevent the primary activated splenic T cells from apoptosis induced by recross-linking of TCR/CD3 complex.Furtherly,we find that the TNF-R2 cross-Linking can induces a death signal to T cells at 48 hours after activation.However,antibodies to CD28, when cross-linked,greatly inhibited apoptosis via TNF-R2.