{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/1249"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/1249","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Type I Interferon Signaling Pathway May Be Involved in Optimal Interleukin-2 Production in CD4+ T Cells","abstract":"Previous studies demonstrate that interferon alpha (IFN-α) promotes human T helper 1 memory development by positively regulating interleukin-2 (IL-2) expression, a hallmark cytokine of central memory CD4⁺ T cells. The present work seeks to delineate how signaling through the interferon alpha/beta receptor promotes IL-2 secretion in murine CD4⁺ T cell. IL-2 provides an essential growth signal to naïve and memory T cells. Examining naïve OT-II interferon alpha-receptor-2 (IFNAR2) knockout CD4⁺ T cells in vitro, we observed conflicting results in secreted IL-2 protein at 72 hours post-stimulation and intracellular IL-2 protein expression at 48 hours post-stimulation. Subsequent studies suggest this was not due to lack of proliferation or an inherit defect in IL-2 secretion. In response to an in vivo vesicular stomatitis virus infection, OT-II IFNAR2 knockout CD4⁺ T cells displayed defective expansion at seven days post-infection. Signaling through the interferon alpha-receptor may enhance IL-2 expression in CD4⁺ T cells, indicating a possible role for downstream transcription factors in sustaining IL-2 expression. Interestingly, CD4⁺ T cells with a carboxy-terminal substitution in the signal transducer of activator of transcription-2 (STAT2) protein may display a similar defect in T cell receptor mediated IL-2 expression. IFNAR2 knockout and STAT2 knock-in splenocytes may display a defect in IL-2 mRNA expression as early as twelve hours post-stimulation. However, IL-2 promoter activity in OT-II IFNAR2 knockout CD4⁺ T cells is insignificantly increased compared to OT-II wild-type cells, suggesting analysis of IL-2 mRNA stability be examined more closely. Preliminary data suggests STAT2 may translocate to the nucleus in response to TCR stimulation in CD4⁺ T cells and could potentially bind to a putative interferon stimulated response element within the IL-2 promoter. Our findings provide insight into how the type I IFN signaling pathway may play a role regulate IL-2 expression in CD4⁺ T cells.","abstract_html":"Previous studies demonstrate that interferon alpha (IFN-α) promotes human T helper 1 memory development by positively regulating interleukin-2 (IL-2) expression, a hallmark cytokine of central memory CD4⁺ T cells. The present work seeks to delineate how signaling through the interferon alpha/beta receptor promotes IL-2 secretion in murine CD4⁺ T cell. IL-2 provides an essential growth signal to naïve and memory T cells. Examining naïve OT-II interferon alpha-receptor-2 (IFNAR2) knockout CD4⁺ T cells in vitro, we observed conflicting results in secreted IL-2 protein at 72 hours post-stimulation and intracellular IL-2 protein expression at 48 hours post-stimulation. Subsequent studies suggest this was not due to lack of proliferation or an inherit defect in IL-2 secretion. In response to an in vivo vesicular stomatitis virus infection, OT-II IFNAR2 knockout CD4⁺ T cells displayed defective expansion at seven days post-infection. Signaling through the interferon alpha-receptor may enhance IL-2 expression in CD4⁺ T cells, indicating a possible role for downstream transcription factors in sustaining IL-2 expression. Interestingly, CD4⁺ T cells with a carboxy-terminal substitution in the signal transducer of activator of transcription-2 (STAT2) protein may display a similar defect in T cell receptor mediated IL-2 expression. IFNAR2 knockout and STAT2 knock-in splenocytes may display a defect in IL-2 mRNA expression as early as twelve hours post-stimulation. However, IL-2 promoter activity in OT-II IFNAR2 knockout CD4⁺ T cells is insignificantly increased compared to OT-II wild-type cells, suggesting analysis of IL-2 mRNA stability be examined more closely. Preliminary data suggests STAT2 may translocate to the nucleus in response to TCR stimulation in CD4⁺ T cells and could potentially bind to a putative interferon stimulated response element within the IL-2 promoter. Our findings provide insight into how the type I IFN signaling pathway may play a role regulate IL-2 expression in CD4⁺ T cells.","abstract_has_math":false,"creators":["Hagan, Kristan Andrea"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Farrar, J. 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The present work seeks to delineate how signaling through the interferon alpha/beta receptor promotes IL-2 secretion in murine CD4⁺ T cell. IL-2 provides an essential growth signal to naïve and memory T cells. Examining naïve OT-II interferon alpha-receptor-2 (IFNAR2) knockout CD4⁺ T cells in vitro, we observed conflicting results in secreted IL-2 protein at 72 hours post-stimulation and intracellular IL-2 protein expression at 48 hours post-stimulation. Subsequent studies suggest this was not due to lack of proliferation or an inherit defect in IL-2 secretion. In response to an in vivo vesicular stomatitis virus infection, OT-II IFNAR2 knockout CD4⁺ T cells displayed defective expansion at seven days post-infection. Signaling through the interferon alpha-receptor may enhance IL-2 expression in CD4⁺ T cells, indicating a possible role for downstream transcription factors in sustaining IL-2 expression. Interestingly, CD4⁺ T cells with a carboxy-terminal substitution in the signal transducer of activator of transcription-2 (STAT2) protein may display a similar defect in T cell receptor mediated IL-2 expression. IFNAR2 knockout and STAT2 knock-in splenocytes may display a defect in IL-2 mRNA expression as early as twelve hours post-stimulation. However, IL-2 promoter activity in OT-II IFNAR2 knockout CD4⁺ T cells is insignificantly increased compared to OT-II wild-type cells, suggesting analysis of IL-2 mRNA stability be examined more closely. Preliminary data suggests STAT2 may translocate to the nucleus in response to TCR stimulation in CD4⁺ T cells and could potentially bind to a putative interferon stimulated response element within the IL-2 promoter. Our findings provide insight into how the type I IFN signaling pathway may play a role regulate IL-2 expression in CD4⁺ T cells."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Type I Interferon Signaling Pathway May Be Involved in Optimal Interleukin-2 Production in CD4+ T Cells"]}]}],"canonical_facts":{"dc:contributor":["Farrar, J. David"],"dc:creator":["Hagan, Kristan Andrea"],"dc:date":["2013-01-17T16:12:14Z","2013-01-17"],"dc:description":["Previous studies demonstrate that interferon alpha (IFN-α) promotes human T helper 1 memory development by positively regulating interleukin-2 (IL-2) expression, a hallmark cytokine of central memory CD4⁺ T cells. The present work seeks to delineate how signaling through the interferon alpha/beta receptor promotes IL-2 secretion in murine CD4⁺ T cell. IL-2 provides an essential growth signal to naïve and memory T cells. Examining naïve OT-II interferon alpha-receptor-2 (IFNAR2) knockout CD4⁺ T cells in vitro, we observed conflicting results in secreted IL-2 protein at 72 hours post-stimulation and intracellular IL-2 protein expression at 48 hours post-stimulation. Subsequent studies suggest this was not due to lack of proliferation or an inherit defect in IL-2 secretion. In response to an in vivo vesicular stomatitis virus infection, OT-II IFNAR2 knockout CD4⁺ T cells displayed defective expansion at seven days post-infection. Signaling through the interferon alpha-receptor may enhance IL-2 expression in CD4⁺ T cells, indicating a possible role for downstream transcription factors in sustaining IL-2 expression. Interestingly, CD4⁺ T cells with a carboxy-terminal substitution in the signal transducer of activator of transcription-2 (STAT2) protein may display a similar defect in T cell receptor mediated IL-2 expression. IFNAR2 knockout and STAT2 knock-in splenocytes may display a defect in IL-2 mRNA expression as early as twelve hours post-stimulation. However, IL-2 promoter activity in OT-II IFNAR2 knockout CD4⁺ T cells is insignificantly increased compared to OT-II wild-type cells, suggesting analysis of IL-2 mRNA stability be examined more closely. Preliminary data suggests STAT2 may translocate to the nucleus in response to TCR stimulation in CD4⁺ T cells and could potentially bind to a putative interferon stimulated response element within the IL-2 promoter. Our findings provide insight into how the type I IFN signaling pathway may play a role regulate IL-2 expression in CD4⁺ T cells."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/1249","841588594"],"dc:subject":["Interferon Type I","CD4-Positive T-Lymphocytes","Receptors, Interleukin-2"],"dc:title":["Type I Interferon Signaling Pathway May Be Involved in Optimal Interleukin-2 Production in CD4+ T Cells"],"dc:type":["Thesis","Text"]},"updated_at":"2026-07-24T05:52:20Z"}