MECHANISMS OF NONSTERILIZING IMMUNITY IN MALARIA

我们研究计划的总体目标是利用小鼠模型 为了阐明由疟原虫激活的T淋巴细胞的生物学， 目的是了解T细胞如何参与保护性免疫 对疟疾的反应。拟议的研究将主要集中在两个方面 细胞免疫中经常被忽视的作用的重要方面 疟疾中的(CMI)：(I)鉴定和鉴定CD4+T细胞 参与对急性疟疾的保护性CMI反应，以及(Ii) 检测γ-增量T细胞作为效应细胞在 抑制寄生虫的生长。来验证我们的假设CD+4 T细胞和 Gamma Delta T细胞协同杀伤或抑制肿瘤生长 疟疾血液期寄生虫，我们将研究其作用 CD_4~+α-βT细胞分化在急性血液病中的作用 P.C.Adami疟疾分期和涉及的免疫激活机制。 这将包括对特定细胞类型产生的细胞因子的研究 用流式细胞仪和聚合酶链式反应技术。的研究 体内的抗原呈递和T细胞分化将使用 将选定的细胞过继转移到新的接受者，II类 缺陷的A0/0基因敲除小鼠。选定的细胞因子在细胞因子中的作用 P.C.Adami疟疾期间的保护和CD4+T细胞分化 细胞因子替代在选择性白细胞介素性基因敲除中的研究 老鼠。抗体介导的耗竭和Gamma Delta T细胞基因敲除小鼠 将被用来确定Gala Delta T细胞是否会增加 在人类和小鼠疟疾中都需要数量，以解决 P.C.阿达米疟疾。此外，其身份和特征 将检查对感染作出反应的Gamma Delta T细胞，并 CD4+T细胞对γ-增量T细胞亚群增殖的调节作用 在急性血液期，将对疟疾进行调查。 这些研究的结果将有助于未来实验的设计。 对我们理解保护性免疫机制至关重要 用于解决人类疟疾的问题。这样的信息可能会被证明是至关重要的 为今后保护性疫苗的设计提供依据 细胞因子治疗利什曼病已被提出。

The overall goal of our research program is to utilize the murine model of malaria to elucidate the biology of T lymphocytes activated by plasmodia, with the aim of understanding how T cells participate in protective immune responses to malaria. The proposed research will focus primarily on two important aspects of the often overlooked role of cell mediated immunity (CMI) in malaria: (i) identification and characterization CD4+ T cells that participate in protective CMI responses to acute malaria, and (ii) examination the role of gamma delta T cells as effector cells in suppressing parasite growth. To test our hypothesis that CD+4 T cells and gamma delta T cells collaborate in killing or inhibiting the growth of malarial parasites during blood-stage malaria, we will examine the role of CD4+ alphabeta T cell differentiation in the resolution of acute blood- stage P. c. adami malaria and the mechanisms of immune activation involved. This will include the study of cytokines produced by specific cell types during infection using flow cytometric and PCR techniques. Studies of antigen presentation and T cell differentiation in vivo will use the adoptive transfer of selected cells to a novel recipient, the Class II deficient A0/0 knockout mouse. The role of selected cytokines in protection and CD4+ T cell differentiation during P. c. adami malaria will be investigated by cytokine replacement in selected interleukin knockout mice. Antibody-mediated depletion and gamma delta T cell knockout mice will be used to determine whether galla delta T cells, which increase in number in both human and murine malaria, are required for the resolution of P. c. adami malaria. In addition, the identity and characteristics of gamma delta T cells responding to infection will be examined and the regulation of the gamma delta T cell subset expansion by CD4+ T cells during acute blood-stage malaria will be investigated. The results of these studies will aid in the design of future experiments crucial to our understanding of protective immune mechanisms responsible for the resolution of malaria in humans. Such information may prove vital in the design of protective vaccines and provide a basis for future cytokine therapy as has been proposed for leishmaniasis.