GROWTH OF B MALAYI IN MURINE MODELS--ROLE OF NK CELLS

在过去的几年里，我们一直在分析布鲁日的病程 在许多小鼠模型中的马来病毒感染。 根据这些研究，我们 提出假设B.马来语要求宿主衍生因子为 在哺乳动物宿主中生长和发育的淋巴起源。 这 这一假说促使我们重新审视人与人之间的相互作用， 免疫系统和B。马来语作为一种动态的双向互动， 而不是纯粹的宿主保护性反应 我们的数据有力地表明 NK细胞是该因子的潜在细胞来源。 在 目前的建议，我们计划通过重复一些来证实我们的假设。 我们的研究，以及评估（1）NK细胞耗竭的影响 在易感动物中和（2）在非允许动物中的NK细胞重建 动物对B生长的影响。马来语。 此外，我们将分析 B损失动力学。马来人在非允许的动物，以确定 在其发展过程中需要生长因子的精确点。 我们还建议建立体外实验，以确定一个细胞系 其将最好地支持B的体外生长和发育。马来语。 使用标准的体细胞遗传技术，我们将分离 细胞系的许多变异体不再支持 的B。马来语。 利用差异显示技术，我们将确定 突变体中缺失的mRNA分子。 识别参与相互作用的分子可能有助于 我们制定了一个合理的免疫预防方法，以及 淋巴丝虫的药理学

Over the past few years, we have been analyzing the course of Brugia malayi infection in numerous murine models. Based on these studies, we propose a hypothsis that B. malayi requires a host derived factor of lymphoid origin for growth and development in the mammalian host. This hypothsis provokes us to re-examine the interaction between the human immune system and B. malayi as a dynamic bi-directional interaction, rather than a pure host protective response. Our data strongly suggest that NK cells are a potential cell source for this factor. In the current proposal, we plan to confirm our hypothesis by repeating some our studies, as well as evaluating the effect of (1) NK cell depletion in susceptible animals and (2) NK cell reconstitution in non-permissive animals on the growth of B. malayi. In addition, we will analyze the kinetics of the loss of B. malayi in non-permissive animals to determine the precise point in its development that the growth factor is required. We also propose to set up in vitro experiments to identify a cell line that will best support the in vitro growth and development of B. malayi. Using standard somatic cell genetic technologies, we will isolate numerous variants from the cell line that no longer support the growth of B. malayi. Using differential display technology, we will determine the mRNA molrcule(s) that is (are) missing in the mutants. Identification of the molecule(s) involved in the interaction could help us formulate a rationale approach to immunoprophylaxis, as well as pharmacology of lymphatic filarial parasites.