TRAIL transduced reverse signals in T cell activation

• Main Authors: WANG, TING-FANG, 王廷芳
• Other Authors: Hsu, Ping-Ning
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/99666307916030568207

碩士 === 國立臺灣大學 === 免疫學研究所 === 90 === TRAIL is a novel member of TNF superfamily molecules, selective induces apoptosis in transformed cell lines, but only with little cytotoxic effect on normal cells. Five TRAIL receptors has been identified and it will transduce signal when engaged with its ligand, TRAIL. Recently studies have found that many TNF superfamily members have ability to transduce reverse signals through ligand itself. Previous studies in our laboratory had proved that TRAIL also can transduce reverse signals after engaging its receptor. According to previous studies in this libratory, it has demonstrated that TRAIL could enhance mouse T cell proliferation after TCR engagement and signal the augmentation of IFNg secretion. To investigate what T cell subsets are involved in TRAIL reverse signals and whether this phenomena also occurs in human PBMC, we isolated both mouse and human CD4+ T cells and CD8+ T cells, stimulated with immobilize DR4-Fc and suboptimal anti-CD3 in vitro. Our results demonstrate that it is CD4+ T cell but not CD8+ T cell responding to TRAIL co-stimulation. Increased production of IFNg is also observed in CD4+ T cells activated with anti-CD3 and DR4. When CD4+ T cells were co-stimulated with TRAIL, there is also increased phosphorylation level of p38 MAP kinase in CD4+ T cells. For further explore the molecules involved in TRAIL reverse signals pathway, we use DR4-Fc to co-immunoprecipitate the possible molecules associated with TRAIL. We were able to detect some possible candidate proteins in Jurkat cells in immunoprecipitation. It still need further characterization to identify the proteins involved in TRAIL reverse signaling. On the other hand, we compared the TRAIL reverse signals with CD28 co-stimulation signals. Our results indicated that CD28 co-stimulation were stronger than TRAIL induced T cell activation at the same level of TCR stimulation in induction of T cell proliferation. To investigate the differences in signal transduction mechanisms between CD28 and TRAIL co-stimulation, we study the tyrosine kinase phosphorylation pattern between T cells activated by CD28 and TRAIL, and we found that there were tyrosine phosphoryaltion induced after TRAIL and CD28 co-stimulation and the phosphorylated tyrosine kinase level were higher in CD28 co-stimulation signals than TRAIL reverse signals. Our results suggest that typrosine kinase may play a role in TRAIL reverse signaling.