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dc.contributor.authorLyon De Ana, Carolinaen_US
dc.date.accessioned2017-09-15T18:02:41Z
dc.date.available2017-09-15T18:02:41Z
dc.date.issued2017
dc.identifier.urihttps://hdl.handle.net/2144/23813
dc.description.abstractCD4 T helper (Th) cells differentiate into distinct effector or regulatory subsets as needed during the course of an infection. Ikaros is a transcription factor that is necessary for proper thymic T cell development. In order to study the role of Ikaros in peripheral CD4 T-cell differentiation and function, a novel Ikaros conditional knockout mouse in which Ikaros is deleted in mature T-cells (CKO mice) was developed. In this thesis, this model is characterized and used to evaluated how absence of Ikaros affects lymphocyte and myeloid populations in vivo, and CD4 T-cell differentiation into T helper 17 (Th17) and inducible regulatory T cell (iTreg) subsets in vitro. CKO mice had normal thymocyte development and normal percentages of T-cells and B-cells in the spleen. However, they had increased percentages of myeloid cells, and an abnormal population of "naive-like" CD4 T-cells that expressed low levels of CD62L and CD44, markers that identify naive and memory T cell populations. CKO CD4 T-cells cultured under Th17 polarizing conditions showed normal expression of the Th17 factors, RORγt and IL-17A, but overexpressed the pro-inflammatory factors T-bet, IFNγ and GM-CSF. CKO CD4 T-cells had a decreased ability to become iTregs as shown by significantly less Foxp3+ CD4+ T-cells in polarizing cultures, and overexpress T-bet, IFNγ and GM-CSF. Therefore, T-cells that lack Ikaros do not properly differentiate into either Th17 or iTreg lineages, but instead become cells with altered pro-inflammatory characteristics. In conclusion, the data highlights new roles of Ikaros in maintaining proper CD4 T-cell populations in the periphery and in suppressing abnormal pro-inflammatory responses.en_US
dc.language.isoen_US
dc.subjectImmunologyen_US
dc.subjectIkarosen_US
dc.subjectT-cellsen_US
dc.titleEvaluation of a conditional knockout of Ikaros in peripheral T-cell differentiation into helper T-cell subsetsen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2017-07-13T01:14:13Z
etd.degree.nameMaster of Scienceen_US
etd.degree.levelmastersen_US
etd.degree.disciplinePathologyen_US
etd.degree.grantorBoston Universityen_US


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