{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/676"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/676","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Reciprocal Regulation of CD4+ and CD8+ T Lymphocyte Effector and Memory Fates by Interleukin 12 and Type 1 Interferon","abstract":"Cytokine signaling networks play an important role in bridging the innate and adaptive immune responses. For example, the innate cytokines Interleukin-12 (IL-12) and type I interferon (IFN-a/b) are induced to high levels by intracellular bacterial and viral infections and have been shown to promote adaptive T lymphocyte responses to infection. While the role for IL-12 on the development of T lymphocyte effector responses has been well characterized, the exact role for IFN-a/b on these responses has been controversial. Therefore, the present study set forth to characterize the distinct roles for IL-12 and IFN-a/b on the development of effector and memory responses in human CD4+ and CD8+ T cells. My work has found that IL-12 drives the development of effector CD4+ and CD8+ T cells. In contrast, IFN-a/b was incapable of promoting these responses and this was due to a difference in the kinetics of activation of two downstream transcription factors STAT4 and T-bet. Further examination of CD8+ T cells revealed a distinct role for IFN-a/b in the development of a population of central memory T cells (TCM). Alternatively, IL-12 drove the development of effector memory cells (TEM). The variegated development of TCM and TEM was dictated by differential cytokine receptor expression and further, the strength of primary T cell receptor (TCR) activation determined the responsiveness to cytokine polarization. Finally, these studies uncovered a novel role for CD8+ T cell licensing of CTL activity through the costimulatory CD27/CD70 pathway. Therefore, taken together, these findings support a novel model in which TCR activation and costimulation act to shape the ability for IL-12 and IFN-a/b to differentially program the development of distinct classes of effector and memory CD8+ T lymphocytes. These studies have direct bearing on the design and development of effective therapeutics and vaccines and demonstrate a new understanding on the modulation of the adaptive immune response to intracellular infection.","abstract_html":"Cytokine signaling networks play an important role in bridging the innate and adaptive immune responses. For example, the innate cytokines Interleukin-12 (IL-12) and type I interferon (IFN-a/b) are induced to high levels by intracellular bacterial and viral infections and have been shown to promote adaptive T lymphocyte responses to infection. While the role for IL-12 on the development of T lymphocyte effector responses has been well characterized, the exact role for IFN-a/b on these responses has been controversial. Therefore, the present study set forth to characterize the distinct roles for IL-12 and IFN-a/b on the development of effector and memory responses in human CD4+ and CD8+ T cells. My work has found that IL-12 drives the development of effector CD4+ and CD8+ T cells. In contrast, IFN-a/b was incapable of promoting these responses and this was due to a difference in the kinetics of activation of two downstream transcription factors STAT4 and T-bet. Further examination of CD8+ T cells revealed a distinct role for IFN-a/b in the development of a population of central memory T cells (TCM). Alternatively, IL-12 drove the development of effector memory cells (TEM). The variegated development of TCM and TEM was dictated by differential cytokine receptor expression and further, the strength of primary T cell receptor (TCR) activation determined the responsiveness to cytokine polarization. Finally, these studies uncovered a novel role for CD8+ T cell licensing of CTL activity through the costimulatory CD27/CD70 pathway. Therefore, taken together, these findings support a novel model in which TCR activation and costimulation act to shape the ability for IL-12 and IFN-a/b to differentially program the development of distinct classes of effector and memory CD8+ T lymphocytes. These studies have direct bearing on the design and development of effective therapeutics and vaccines and demonstrate a new understanding on the modulation of the adaptive immune response to intracellular infection.","abstract_has_math":false,"creators":["Ramos, Hilario Jose"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Farrar, J. 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For example, the innate cytokines Interleukin-12 (IL-12) and type I interferon (IFN-a/b) are induced to high levels by intracellular bacterial and viral infections and have been shown to promote adaptive T lymphocyte responses to infection. While the role for IL-12 on the development of T lymphocyte effector responses has been well characterized, the exact role for IFN-a/b on these responses has been controversial. Therefore, the present study set forth to characterize the distinct roles for IL-12 and IFN-a/b on the development of effector and memory responses in human CD4+ and CD8+ T cells. My work has found that IL-12 drives the development of effector CD4+ and CD8+ T cells. In contrast, IFN-a/b was incapable of promoting these responses and this was due to a difference in the kinetics of activation of two downstream transcription factors STAT4 and T-bet. Further examination of CD8+ T cells revealed a distinct role for IFN-a/b in the development of a population of central memory T cells (TCM). Alternatively, IL-12 drove the development of effector memory cells (TEM). The variegated development of TCM and TEM was dictated by differential cytokine receptor expression and further, the strength of primary T cell receptor (TCR) activation determined the responsiveness to cytokine polarization. Finally, these studies uncovered a novel role for CD8+ T cell licensing of CTL activity through the costimulatory CD27/CD70 pathway. Therefore, taken together, these findings support a novel model in which TCR activation and costimulation act to shape the ability for IL-12 and IFN-a/b to differentially program the development of distinct classes of effector and memory CD8+ T lymphocytes. These studies have direct bearing on the design and development of effective therapeutics and vaccines and demonstrate a new understanding on the modulation of the adaptive immune response to intracellular infection."]},{"key":"dc:format","label":"Dc Format","values":["Electronic","application/pdf","born digital"]},{"key":"dc:title","label":"Title","values":["Reciprocal Regulation of CD4+ and CD8+ T Lymphocyte Effector and Memory Fates by Interleukin 12 and Type 1 Interferon"]}]}],"canonical_facts":{"dc:contributor":["Farrar, J. David"],"dc:creator":["Ramos, Hilario Jose"],"dc:date":["2010-07-12T18:49:07Z","2009-06-18"],"dc:description":["Cytokine signaling networks play an important role in bridging the innate and adaptive immune responses. For example, the innate cytokines Interleukin-12 (IL-12) and type I interferon (IFN-a/b) are induced to high levels by intracellular bacterial and viral infections and have been shown to promote adaptive T lymphocyte responses to infection. While the role for IL-12 on the development of T lymphocyte effector responses has been well characterized, the exact role for IFN-a/b on these responses has been controversial. Therefore, the present study set forth to characterize the distinct roles for IL-12 and IFN-a/b on the development of effector and memory responses in human CD4+ and CD8+ T cells. My work has found that IL-12 drives the development of effector CD4+ and CD8+ T cells. In contrast, IFN-a/b was incapable of promoting these responses and this was due to a difference in the kinetics of activation of two downstream transcription factors STAT4 and T-bet. Further examination of CD8+ T cells revealed a distinct role for IFN-a/b in the development of a population of central memory T cells (TCM). Alternatively, IL-12 drove the development of effector memory cells (TEM). The variegated development of TCM and TEM was dictated by differential cytokine receptor expression and further, the strength of primary T cell receptor (TCR) activation determined the responsiveness to cytokine polarization. Finally, these studies uncovered a novel role for CD8+ T cell licensing of CTL activity through the costimulatory CD27/CD70 pathway. Therefore, taken together, these findings support a novel model in which TCR activation and costimulation act to shape the ability for IL-12 and IFN-a/b to differentially program the development of distinct classes of effector and memory CD8+ T lymphocytes. These studies have direct bearing on the design and development of effective therapeutics and vaccines and demonstrate a new understanding on the modulation of the adaptive immune response to intracellular infection."],"dc:format":["Electronic","application/pdf","born digital"],"dc:identifier":["https://hdl.handle.net/2152.5/676","754646349"],"dc:language":["en"],"dc:subject":["Interferon-alpha","Immunologic Memory","CD8-Positive T-Lymphocytes","Interleukin-12"],"dc:title":["Reciprocal Regulation of CD4+ and CD8+ T Lymphocyte Effector and Memory Fates by Interleukin 12 and Type 1 Interferon"],"dc:type":["Thesis","Text","dissertation"]},"updated_at":"2026-07-24T05:52:20Z"}