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This dissertation, A Study of the Expression of Sonic Hedgehog and Its Receptors in T Cells and the Identification of Sonic Hedgehog Dowm-stream Targets in Activated CD4 T Cells by Suk-yi, Chau, 周淑怡, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled A study of the expression of Sonic hedgehog and its receptors in T cells and the identification of Sonic hedgehog down-stream targets in activated CD4 T cells Submitted by Suk Yi CHAU for the degree of Master of Philosophy at The University of Hong Kong in August 2004 Sonic hedgehog (Shh) is a crucial morphogenic factor for the development of many tissues and organs including the nervous system, gastrointestinal track, lung and hair. Shh signal has been implicated in the tumorigenesis of basal cell carcinoma and medulloblastoma. Recent studies have also suggested an important role of Shh in thymocyte development and mature T cell functions. However, the down-stream targets of Shh signaling in T cells are unknown. Furthermore, the expression pattern of Shh and its receptors in T lymphocytes has not been systematically examined. In this study, the following objectives were set out to address the above aspects: (1) to investigate the expression profile of Shh and its receptors in resting and activated T cells; (2) to study the distribution of Shh and its receptors during TCR clustering; and (3) to verify potential down-stream targets of Shh in activated CD4 T cells from microarray analysis. Using immunostaining and quantitative RT-PCR, Shh and its receptors, Patched and Smoothened, were + + shown to be expressed on both CD4 and CD8 T cells. Furthermore, their expression pattern changed upon T cell activation. As Shh can potentiate T cell activation, much like CD28, it may act as a co-stimulatory factor for T cell activation. However, the study on the distribution of Shh and its receptors during TCR clustering showed that Shh and its receptors were not co-localized with in vitro TCR capping. This shows that Shh potentiates T cell activation and proliferation through a different mechanism when compared with other co-stimulatory molecules found in the immunological synapse, such as CD28. In the verification of down-stream targets of Shh in activated CD4 T cells, Cyclin A and B-cell translocation gene 2 mRNA expressions were both modulated by Shh and CD28 signaling. However, CD28 regulated genes, including Bcl-xL, CIS and Cyclin E2, were not affected by Shh signaling. These results show that Shh may share some but not all down-stream target genes with the CD28 pathway. The down-stream mechanism of enhancement on T cell activation of the two pathways is therefore likely different. DOI: 10.5353/th_b3138623 Subjects: Protein precursorsCellular signal transductionT cellsGene expressionCytogenetics

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