AuthorsLucas, Julie Ann
Faculty AdvisorDr. Leslie J. Berg
Academic ProgramImmunology and Microbiology
UMass Chan AffiliationsPathology
Document TypeDoctoral Dissertation
Animal Experimentation and Research
Enzymes and Coenzymes
Hemic and Immune Systems
MetadataShow full item record
AbstractItk is a member of the Tec family of non-receptor tyrosine kinases. It is expressed in T cells, NK cells, and mast cells. The purpose of this study was to determine the role of Itk in T cell development. Previous work from our lab and others has demonstrated that Itk is involved in signaling downstream of the T cell receptor and initial analysis of Itk-deficient mice revealed that these mice had some defects in T cell development. There are two stages of T cell development, the pre-T cell stage and the CD4+ CD8+ double positive stage, at which signals downstream of the T cell receptor are important. At the CD4+ CD8+ double positive stage, these signals direct two concurrent, but distinct processes known as repertoire selection and CD4/CD8 lineage commitment/differentiation. I show that there are only slight defects in development at the pre-T cell stage, presumably due to reduced TCR signaling. However these results clearly demonstrate that Itk is not essential at this stage of development. In contrast, repertoire selection, in particular positive selection, is significantly affected by the absence of Itk. Similarly, I show that Itk plays a role in lineage differentiation, although commitment to the appropriate lineage occurs normally in the absence of Itk.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/32290
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