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dc.contributor.authorHenderson, Sonja Christine
dc.date.accessioned2014-03-05T16:08:06Z
dc.date.available2014-03-05T16:08:06Z
dc.date.issued2002-05
dc.identifier.otherhenderson_sonja_c_200205_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/henderson_sonja_c_200205_phd
dc.identifier.urihttp://hdl.handle.net/10724/29591
dc.description.abstractWe demonstrate that Ly-6A.2 expression on T cells inhibits their growth, both in the thymus and periphery. The growth inhibitory effects observed in the thymus occur when Ly-6A.2 is expressed ectopically on developing cells that normally do not express this protein. Diminished amount of LAT in the CD4 - CD8 - double negative (DN) subset, enhanced apoptosis of the CD4 + CD8 + double positive (DP) cells and altered selected TCR-V â repertoire is observed in Ly-6A.2 dysregulated thymocytes. These results also suggest the importance of regulated expression of Ly-6A.2 on developing T cells and also provides clues related to the mechanism underlying the thymic block. Ly-6A.2 exerts antigen-specific growth inhibitory effects on CD4 + peripheral T cells when precociously over-expressed on the cell surface. CD4 T expressing dysregulated Ly-6A.2 cells exhibited reduced Ca 2+ flux upon stimulation, indicating membrane proximal events were altered. A major significance of these observations is that Ly-6A.2 might regulate clonal expansion of CD4 + T cells induced by a foreign antigen. Surprisingly, Ly-6A.2 over-expression on CD4 + T cells generates a Th2 promoting factor, IL-4, and may therefore play a role in Th2 differentiation.|The chance observation that ectopic expression of Ly-6A.2 in MHC I and II-deficient mice rescued the CD4 + T cell population was intriguing and provided a golden opportunity to examine the nature of the T cell repertoire that exists prior to positive and negative selection. We were surprised to note that the pre-selected T cell repertoire exhibited considerable reactivity to MHC. These observations might explain the phenonmenon of allogenic reactivity by mature CD4 + T cells.
dc.languageRole of Ly-6A.2 expression in regulating growth of T cells in the thymus and periphery
dc.publisheruga
dc.rightspublic
dc.subjectLy-6A.2
dc.subjectThymus
dc.subjectDevelopment
dc.subjectActivation
dc.subjectInhibition
dc.subjectLinker for Activation of T cells (LAT)
dc.subjectp56lck
dc.subjectTCR
dc.subjectTCR-Vb
dc.subjectMajor-Histocompatibility (MHC)
dc.subjectCD4
dc.subjectCD8
dc.subjectCytokine
dc.subjectInterleukin-4 (IL-4)
dc.subjectTransgenic (Tg)
dc.titleRole of Ly-6A.2 expression in regulating growth of T cells in the thymus and periphery
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentCellular Biology
dc.description.majorCellular Biology
dc.description.advisorAnil K. Bamezai
dc.description.committeeAnil K. Bamezai
dc.description.committeeMary Bedell
dc.description.committeeRaymond Damian
dc.description.committeeDonald Evans
dc.description.committeeRick Tarleton


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