IL-12 as an immunopotentiator in leishmaniasis
IL-12 作为利什曼病的免疫增强剂
基本信息
- 批准号:7581926
- 负责人:
- 金额:$ 39.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1994
- 资助国家:美国
- 起止时间:1994-09-01 至 2013-11-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAntigensApoptosisApoptoticArtsAttenuatedC57BL/6 MouseCD4 Positive T LymphocytesCell SurvivalCellsCharacteristicsDendritic CellsDevelopmentDiseaseEffector CellExperimental ModelsFailureFoundationsFundingGenerationsGoalsHandHome environmentHomingHumanImmuneImmune responseImmunityImmunologic AdjuvantsImmunologic MemoryInfectionInterleukin 7 ReceptorInterleukin-10Interleukin-12Interleukin-4Interleukin-7LeishmaniaLeishmania majorLeishmaniasisLifeListeriaMaintenanceMediatingMemoryModelingMusParasitesPhenotypePlayPopulationPopulation HeterogeneityPublic HealthRegulationResidual stateRoleT memory cellT-Cell DevelopmentT-LymphocyteTh1 CellsTimeTissuesVaccinationVaccine DesignVaccinesantigen Lchemotherapycytokinedisorder controllymph nodesmemory CD4 T lymphocytepathogenpublic health relevanceresearch studyresponsetooltranscription factorvaccine development
项目摘要
DESCRIPTION (provided by applicant): Leishmaniasis is a major public health problem in large parts of the world, due in part to the lack of a vaccine and inadequate chemotherapy. Studies of the immune responses in humans and mice following Leishmania infection have provided an understanding of many of the cells and cytokines that contribute to the control of this disease. Nevertheless, a vaccine for human leishmaniasis does not exist. Understanding how memory T cells develop will be crucial in the development of such vaccines. Two types of memory T cells have been described: T effector memory cells, which produce effector cytokines and migrate through the tissues, and central memory T cells that do not produce effector cytokines and migrate through lymph nodes. C57BL/6 mice infected with Leishmania major are immune to rechallenge after they resolve their infections, but this immunity was thought to be dependent upon residual parasites. Now an attenuated L. major parasite that is eliminated after eight weeks has been shown to stimulate the development of long-lived protective memory T cells. These cells have the characteristics of central memory T cells, and the studies in this proposal will characterize these cells and assess whether we can generate memory T cells with an effector phenotype. The studies will include a comparison of the ability of a Listeria expressing a leishmanial antigen and L. major to stimulate effector memory T cells, assessment of the role that parasite persistence plays in blocking the development of effector memory cells, and how dendritic cells influence memory T cell generation. The experiments utilize state-of-the art tools that will allow qualitative and quantitative assessment of memory T cell development. Overall, the experiments described in this proposal will determine what type of immunologic memory can be induced in leishmaniasis, which will provide direction for the field in establishing what are reasonable goals for a leishmaniasis vaccine. PUBLIC HEALTH RELEVANCE The development of a vaccine for human leishmaniasis is a major priority, but our understanding of how to stimulate the memory T cells required for vaccine-immunity is limited. This proposal will determine how memory T cells develop, are maintained and are regulated using an experimental model of the disease. The results from these experiments will provide a foundation for the development of a successful leishmaniasis vaccine.
描述(由申请人提供):利什曼病在世界大部分地区是一个主要的公共卫生问题,部分原因是缺乏疫苗和化疗不充分。对人类和小鼠感染利什曼原虫后免疫反应的研究,使我们了解了许多有助于控制该病的细胞和细胞因子。然而,人类利什曼病的疫苗还不存在。了解记忆T细胞是如何发育的,对开发这类疫苗至关重要。有两种类型的记忆T细胞被描述为:T效应记忆细胞,产生效应细胞因子并通过组织迁移;中枢记忆T细胞,不产生效应细胞因子并通过淋巴结迁移。感染利什曼原虫的C57BL/6小鼠在感染消退后对再攻毒具有免疫力,但这种免疫力被认为依赖于残留的寄生虫。现在,一种减毒的L. major寄生虫在8周后被消灭,已经被证明可以刺激长寿命保护性记忆T细胞的发育。这些细胞具有中枢记忆T细胞的特征,本提案的研究将对这些细胞进行表征,并评估我们是否可以产生具有效应表型的记忆T细胞。这些研究将包括比较表达利什曼抗原和L. major的李斯特菌刺激效应记忆T细胞的能力,评估寄生虫持久性在阻断效应记忆细胞发育中的作用,以及树突状细胞如何影响记忆T细胞的产生。实验利用最先进的工具,将允许记忆T细胞发展的定性和定量评估。总的来说,本提案中描述的实验将确定在利什曼病中可以诱导哪种类型的免疫记忆,这将为该领域确定利什曼病疫苗的合理目标提供方向。人类利什曼病疫苗的开发是一个主要的优先事项,但我们对如何刺激疫苗免疫所需的记忆T细胞的理解有限。这一建议将确定记忆T细胞如何发展,维持和调节使用疾病的实验模型。这些实验的结果将为研制成功的利什曼病疫苗奠定基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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PHILLIP SCOTT其他文献
PHILLIP SCOTT的其他文献
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{{ truncateString('PHILLIP SCOTT', 18)}}的其他基金
2023 Woods Hole Immunoparasitology Meeting
2023 年伍兹霍尔免疫寄生虫学会议
- 批准号:
10680864 - 财政年份:2023
- 资助金额:
$ 39.38万 - 项目类别:
2022 WOODS HOLE IMMUNOPARASITOLOGY MEETING
2022 年伍兹霍尔免疫寄生虫学会议
- 批准号:
10458244 - 财政年份:2022
- 资助金额:
$ 39.38万 - 项目类别:
CD8 T cell-dependent pathways leading to immunopathology in cutaneous leishmaniasis
CD8 T 细胞依赖性途径导致皮肤利什曼病的免疫病理学
- 批准号:
10329958 - 财政年份:2020
- 资助金额:
$ 39.38万 - 项目类别:
CD8 T cell-dependent pathways leading to immunopathology in cutaneous leishmaniasis
CD8 T 细胞依赖性途径导致皮肤利什曼病的免疫病理学
- 批准号:
10556387 - 财政年份:2020
- 资助金额:
$ 39.38万 - 项目类别:
23rd Annual Woods Hole Immunoparasitology (WHIP) Meeting
第 23 届伍兹霍尔免疫寄生虫学 (WHIP) 年度会议
- 批准号:
9750405 - 财政年份:2019
- 资助金额:
$ 39.38万 - 项目类别:
20th Annual Woods Hole Immunoparasitology Meeting
第 20 届伍兹霍尔免疫寄生虫学年度会议
- 批准号:
9126050 - 财政年份:2016
- 资助金额:
$ 39.38万 - 项目类别:
Annual Woods Hole Immunoparasitology (WHIP) Meeting
年度伍兹霍尔免疫寄生虫学 (WHIP) 会议
- 批准号:
8899229 - 财政年份:2015
- 资助金额:
$ 39.38万 - 项目类别:
Protective and Pathologic Roles for CD8+ T cells in Leishmaniasis
CD8 T 细胞在利什曼病中的保护和病理作用
- 批准号:
8758136 - 财政年份:2014
- 资助金额:
$ 39.38万 - 项目类别:
Protective and Pathologic Roles for CD8+ T cells in Leishmaniasis
CD8 T 细胞在利什曼病中的保护和病理作用
- 批准号:
8895257 - 财政年份:2014
- 资助金额:
$ 39.38万 - 项目类别:
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