The Role of PML in T cell Activation and Apoptosis

• Main Authors: Wan-ni Yu, 兪宛妮
• Other Authors: Ming-Zone Lai
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/03996022729132045932

碩士 === 國立臺灣大學 === 免疫學研究所 === 90 === Abstract Promyelocytic leukemia (PML) protein is found concentrated in nuclear body along with other proteins including pRB, P53, Daxx, CBP and SUMO-1. Various functions have been attributed to the PML nuclear body, but the exact biochemical mechanism is still unclear. PML is known to involve in cell growth, tumor suppression, apoptosis, and immune response. Here we investigated the role of PML on T cell development, T cell activation, and T cell apoptosis by transgenic expression of PML and PML△3K. We generated transgenic mice expressing PML or PML△3K under the control of the T cell-specific CD2 promoter. In PML transgenic mice, total thymocyte number and splenocyte number remained normal. The frequency of double-negative, double-positive and single-positive thymocytes was similar between PML transgenic and wild-type mice. In addition, within the double-negative thymocytes, the development of CD44+CD25-, CD44+CD25+, CD44-CD25+ and CD44-CD25- was normal. Positive selection was not affected in thymocytes of PML transgenic mice. Levels of TCR expression were also indistinquishable between wild-type and PML transgenic mice. There was an increase in splenic CD4+ population of the PML transgenic mice, yet TCR expression on splenocytes was identical between PML transgenic and wild-type mice. Thymocytes from PML transgenic mice were equally sensitive to Fas-induced apoptosis as wild-type. The proliferation of the PML transgenic thymocytes and splenic T cell were normal. For PML△3K transgenic mice, total thymocyte number and splenocyte number remained normal. PML△3K transgenic mice were normal in thymocyte subsets, thymic positive selection, splenocyte subsets, and sensitivity to Fas-induced cell death. The only defect observed within PML△3K transgenic mice was reduced proliferation in thymocytes. The proliferation of PML△3K splenic T cell, however, was normal. Our results suggest that endogenous level of PML is sufficient to maintain normal T cell development and activation, which is mostly unaffected by PML overexpression. In contrast, proper sumoylation of PML is likely essential for T cell activation, inhibit of PML sumoylation ( and nuclear body localization ) interfered with T cell proliferation.