IL-12 as an immunopotentiator in leishmaniasis

IL-12 作为利什曼病的免疫增强剂

• 批准号: 8197013
• 负责人: PHILLIP SCOTT
• 金额: $ 38.59万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/8197013
• 关键词: Accounting; Address; Antigens; Apoptosis; Apoptotic; Attenuated; C57BL/6 Mouse; CD4 Positive T Lymphocytes; Cell Survival; Cells; Characteristics; Dendritic Cells; Development; Disease; Effector Cell; Experimental Models; Failure; Foundations; Funding; Generations; Goals; Home environment; Homing; Human; Immune; Immune response; Immunity; Immunologic Adjuvants; Immunologic Memory; Infection; Interferons; Interleukin-10; Interleukin-12; Interleukin-4; Interleukin-7; Leishmania; Leishmania major; Leishmaniasis; Life; Listeria; Maintenance; Mediating; Memory; Modeling; Mus; Parasites; Phenotype; Play; Population; Population Heterogeneity; Public Health; Regulation; Residual state; Role; T memory cell; T-Cell Development; T-Lymphocyte; Th1 Cells; Time; Tissues; Vaccination; Vaccine Design; Vaccines; antigen L; chemotherapy; cytokine; disorder control; lymph nodes; memory CD4 T lymphocyte; pathogen; receptor; research study; response; tool; transcription factor; vaccine development

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.

利什曼病是世界大部分地区的一个主要公共卫生问题，部分原因是缺乏预防措施。 疫苗和化疗不足。人类和小鼠免疫反应的研究 利什曼原虫感染提供了许多细胞和细胞因子的理解，有助于 控制这种疾病。然而，人类利什曼病的疫苗并不存在。理解 记忆T细胞如何发育将是这类疫苗开发的关键。两种记忆T T效应记忆细胞，其产生效应细胞因子并通过 组织和不产生效应细胞因子并通过淋巴迁移的中央记忆T细胞 结感染硕大利什曼原虫的C57 BL/6小鼠在解决其免疫应答后对再攻击具有免疫力。 感染，但这种免疫力被认为是依赖于残留的寄生虫。现在是一个弱化的L 八周后被消除的主要寄生虫已被证明可以刺激长- 存活的保护性记忆T细胞这些细胞具有中央记忆T细胞的特征， 这项计划中的研究将描述这些细胞的特征，并评估我们是否可以产生记忆T细胞。 具有效应子表型。这些研究将包括比较李斯特菌表达 利什曼原虫抗原和L.主要刺激效应记忆T细胞，评估寄生虫的作用， 持久性在阻断效应记忆细胞的发育中起作用，以及树突状细胞如何影响 记忆T细胞生成。这些实验利用最先进的工具，将允许定性和定量分析。 记忆T细胞发育的定量评估。总的来说，本提案中描述的实验 将确定什么类型的免疫记忆可以诱导利什曼病，这将提供 为该领域确定什么是利什曼病疫苗的合理目标提供指导。