{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/645"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/645","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Regulation of Effector and Memory Development of Human CD4+ T Cells by Interleukin 12 and Type I Interferon","abstract":"Innate cytokines induced at the onset of infection regulate the development of adaptive immune responses such as CD4+ T helper cell development. For instance, the innate cytokines interleukin 12 (IL-12) and type I interferon (IFN-alpha/beta) are produced in response to intracellular bacterial and viral infections. While the effects of IL-12 on CD4+ T cell differentiation are relatively well-understood, the role of IFN-alpha/beta, despite extensive study, has remained controversial. The present work seeks to clarify the effects of IFN-alpha/beta on CD4+ T cell development, effector functions, and memory generation. Previous reports had suggested that IFN-alpha, like IL-12, could promote Th1 development in human CD4+ T cells. However, my work demonstrates that IFN-alpha is insufficient to induce Th1 differentiation because of an inability to maintain stable STAT4 phosphorylation or T-bet expression. Furthermore, IL-12, but not IFN-alpha, induces the secretion of IFN-gamma and TNF-alpha from human CD4+ T cells. These two cytokines, in addition to promoting bacterial clearance, can directly participate in antiviral immunity via a signaling pathway which involves the type I IFN receptor. Finally, a combination of IL-12 and IFN-alpha influences memory CD4+ T cell function by strongly inducing IL-2 secretion from a subset of cells in a T-bet-independent manner. These IL-2-producing cells demonstrate both phenotypic and functional characteristics of long-lived and pluripotent central memory. Taken together, these data provide a new understanding of the role of innate cytokines in shaping adaptive CD4+ T cell responses. Given the numerous medical uses of IFN-alpha/beta, these findings could have a broad impact on the design of vaccines and antiviral therapeutics.","abstract_html":"Innate cytokines induced at the onset of infection regulate the development of adaptive immune responses such as CD4+ T helper cell development. For instance, the innate cytokines interleukin 12 (IL-12) and type I interferon (IFN-alpha/beta) are produced in response to intracellular bacterial and viral infections. While the effects of IL-12 on CD4+ T cell differentiation are relatively well-understood, the role of IFN-alpha/beta, despite extensive study, has remained controversial. The present work seeks to clarify the effects of IFN-alpha/beta on CD4+ T cell development, effector functions, and memory generation. Previous reports had suggested that IFN-alpha, like IL-12, could promote Th1 development in human CD4+ T cells. However, my work demonstrates that IFN-alpha is insufficient to induce Th1 differentiation because of an inability to maintain stable STAT4 phosphorylation or T-bet expression. Furthermore, IL-12, but not IFN-alpha, induces the secretion of IFN-gamma and TNF-alpha from human CD4+ T cells. These two cytokines, in addition to promoting bacterial clearance, can directly participate in antiviral immunity via a signaling pathway which involves the type I IFN receptor. Finally, a combination of IL-12 and IFN-alpha influences memory CD4+ T cell function by strongly inducing IL-2 secretion from a subset of cells in a T-bet-independent manner. These IL-2-producing cells demonstrate both phenotypic and functional characteristics of long-lived and pluripotent central memory. Taken together, these data provide a new understanding of the role of innate cytokines in shaping adaptive CD4+ T cell responses. Given the numerous medical uses of IFN-alpha/beta, these findings could have a broad impact on the design of vaccines and antiviral therapeutics.","abstract_has_math":false,"creators":["Davis, Ann Marie"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Farrar, J. David"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-07-12T18:43:15Z","date_published":"2010-07-12T18:43:15Z","updated_at":"2026-07-24T05:52:17Z","subjects":["CD4-Positive T-Lymphocytes","Immunologic Memory","Interferon-alpha"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["759853519"],"render_values":[{"text":"759853519","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/645","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Farrar, J. 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For instance, the innate cytokines interleukin 12 (IL-12) and type I interferon (IFN-alpha/beta) are produced in response to intracellular bacterial and viral infections. While the effects of IL-12 on CD4+ T cell differentiation are relatively well-understood, the role of IFN-alpha/beta, despite extensive study, has remained controversial. The present work seeks to clarify the effects of IFN-alpha/beta on CD4+ T cell development, effector functions, and memory generation. Previous reports had suggested that IFN-alpha, like IL-12, could promote Th1 development in human CD4+ T cells. However, my work demonstrates that IFN-alpha is insufficient to induce Th1 differentiation because of an inability to maintain stable STAT4 phosphorylation or T-bet expression. Furthermore, IL-12, but not IFN-alpha, induces the secretion of IFN-gamma and TNF-alpha from human CD4+ T cells. These two cytokines, in addition to promoting bacterial clearance, can directly participate in antiviral immunity via a signaling pathway which involves the type I IFN receptor. Finally, a combination of IL-12 and IFN-alpha influences memory CD4+ T cell function by strongly inducing IL-2 secretion from a subset of cells in a T-bet-independent manner. These IL-2-producing cells demonstrate both phenotypic and functional characteristics of long-lived and pluripotent central memory. Taken together, these data provide a new understanding of the role of innate cytokines in shaping adaptive CD4+ T cell responses. Given the numerous medical uses of IFN-alpha/beta, these findings could have a broad impact on the design of vaccines and antiviral therapeutics."]},{"key":"dc:format","label":"Dc Format","values":["Electronic","application/pdf","born digital"]},{"key":"dc:title","label":"Title","values":["Regulation of Effector and Memory Development of Human CD4+ T Cells by Interleukin 12 and Type I Interferon"]}]}],"canonical_facts":{"dc:contributor":["Farrar, J. David"],"dc:creator":["Davis, Ann Marie"],"dc:date":["2010-07-12T18:43:15Z","2009-01-09"],"dc:description":["Innate cytokines induced at the onset of infection regulate the development of adaptive immune responses such as CD4+ T helper cell development. For instance, the innate cytokines interleukin 12 (IL-12) and type I interferon (IFN-alpha/beta) are produced in response to intracellular bacterial and viral infections. While the effects of IL-12 on CD4+ T cell differentiation are relatively well-understood, the role of IFN-alpha/beta, despite extensive study, has remained controversial. The present work seeks to clarify the effects of IFN-alpha/beta on CD4+ T cell development, effector functions, and memory generation. Previous reports had suggested that IFN-alpha, like IL-12, could promote Th1 development in human CD4+ T cells. However, my work demonstrates that IFN-alpha is insufficient to induce Th1 differentiation because of an inability to maintain stable STAT4 phosphorylation or T-bet expression. Furthermore, IL-12, but not IFN-alpha, induces the secretion of IFN-gamma and TNF-alpha from human CD4+ T cells. These two cytokines, in addition to promoting bacterial clearance, can directly participate in antiviral immunity via a signaling pathway which involves the type I IFN receptor. Finally, a combination of IL-12 and IFN-alpha influences memory CD4+ T cell function by strongly inducing IL-2 secretion from a subset of cells in a T-bet-independent manner. These IL-2-producing cells demonstrate both phenotypic and functional characteristics of long-lived and pluripotent central memory. Taken together, these data provide a new understanding of the role of innate cytokines in shaping adaptive CD4+ T cell responses. Given the numerous medical uses of IFN-alpha/beta, these findings could have a broad impact on the design of vaccines and antiviral therapeutics."],"dc:format":["Electronic","application/pdf","born digital"],"dc:identifier":["https://hdl.handle.net/2152.5/645","759853519"],"dc:language":["en"],"dc:subject":["CD4-Positive T-Lymphocytes","Immunologic Memory","Interferon-alpha"],"dc:title":["Regulation of Effector and Memory Development of Human CD4+ T Cells by Interleukin 12 and Type I Interferon"],"dc:type":["Thesis","Text","dissertation"]},"updated_at":"2026-07-24T05:52:17Z"}