Molecular Regulation of Interferon Gamma in 2B4-Activated Natural Killer Cells: Functional Role in Tumor Rejection

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dc.contributor.advisorMathew, Porunellor A.
dc.contributor.committeeMemberGoldfarb, Ronald H.
dc.contributor.committeeMemberDimitrijevich, S. Dan
dc.creatorJohnson, Lori Ann
dc.date.accessioned2019-08-22T21:15:49Z
dc.date.available2019-08-22T21:15:49Z
dc.date.issued2001-11-01
dc.date.submitted2013-08-27T13:28:54-07:00
dc.description.abstractNatural killer cells are a third population of lymphocytes, distinct from T and B cells. NK cells are non-MHC-restricted cytotoxic effector cells which are effective against intracellular pathogens, virally-infected cells and tumor cells. 2B4 is a natural killer cell receptor originally identified in the mouse as a surface molecule involved in non-MHC-restricted killing and enhancement of IFN-γ secretion. The human and rat homologues of 2B4 have recently been cloned in our laboratory. Interferon gamma (IFN-γ) is a cytokine with potent anti-viral and anti-proliferative effects. In addition, this cytokine acts as a global immune regulator by regulating gene expression and serving to attract other immune cells. In this work, we establish the function of human 2B4 in a NK cell line, YT. We have shown that human 2B4 activation induces cytolytic function and enhances IFN-γ release in YT cells. Additionally we show that 2B4’s regulation of IFN-γ occurs at the transcriptional level, both through mRNA stability and increased promoter activity. We also demonstrate that several regions in the IFN-γ promoter respond to 2B4 activation and IFN-γ both separately and together in the rejection of metastatictumor cells in C57B7/6 mice. Our results confirm that both 2B4 and IFN-γ are critical in the rejection of metastatic tumor cells. Through the use of activating monoclonal antibodies, our studies indicate that 2B4’s anti-tumor activity is through IFN-γ as well as through cytolytic function of NK cells.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29198
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectBiology
dc.subjectCell Anatomy
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectCells
dc.subjectCellular and Molecular Physiology
dc.subjectGenetic Phenomena
dc.subjectGenetics and Genomics
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedical Cell Biology
dc.subjectMedical Genetics
dc.subjectMedical Molecular Biology
dc.subjectMedicine and Health Sciences
dc.subjectMolecular Biology
dc.subjectOther Cell and Developmental Biology
dc.subjectNatural killer cells
dc.subjectlymphocytes
dc.subjectnon-MHC-restricted cytotoxic effector cells
dc.subjectIFN-y secretion
dc.subjecthuman homologues
dc.subjectrat homologues
dc.subject2B4
dc.subjectinterferon gamma
dc.subjectcytokine
dc.subjectanti-viral
dc.subjectanti-proliferative
dc.subjectmRNA stability
dc.subjectanti-tumor activity
dc.titleMolecular Regulation of Interferon Gamma in 2B4-Activated Natural Killer Cells: Functional Role in Tumor Rejection
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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