MECHANISMS OF NONSTERILIZING IMMUNITY IN MALARIA

拟议研究的总体目标是调查 由鼠疟原虫激活的T淋巴细胞的生物学， 了解这些细胞如何参与保护性免疫 疟疾期间的反应。 特别是，注意力将集中在 抗体非依赖性细胞介导的保护性免疫应答 导致寄生虫死亡或生长抑制。 抗原特异 保护性T细胞克隆，包括CTR2.1和其他 对P. chabaudi adami和P. vinckei都有明显的抑制作用 petteri和B。利用体外培养技术， 测试它们在体内对同源 和异源寄生虫通过过继转移到 组织相容性裸鼠。 保护性和非保护性T细胞 克隆将根据表面抗原进行表征， 淋巴因子的产生、抗原特异性和 努力确定保护性的独特特征， 克隆T细胞 此外，还将进行实验， 表征保护性T细胞克隆的生物学功能 在体外和体内，以确定它们是否杀死 寄生虫通过释放特定介质或激活 共同耐药途径中的其他细胞类型。 努力 也将确定疟疾的功能- 保护性克隆T细胞可以通过T细胞展示 抗原特异性抑制活性。

The overall goal of the proposed research is to investigate the biology of T lymphocytes activated by murine plasmodia with the aim of understanding how these cells participate in protective immune response during malaria. In particular, attention will be focused on antibody-independent cell mediated protective immune responses leading to parasite death or growth inhibition. Antigen-specific protective T-cell clones including CTR2.1 and others to be developed against P. chabaudi adami as well as against P. vinckei petteri and B. microti utilizing in vitro culture techniques will be tested for their protective activity in vivo against homologous and heterologous parasites by means of adoptive transfer into histocompatible nude mice. Protective and nonprotective T-cell clones will be characterized according to surface antigens, lymphokine production, antigenic specificity, and trafficking in an effort to identify characteristics distinctive of protective cloned T cells. In addition, experiments will be undertaken to characterize the biological function of protective T-cell clones both in vitro and in vivo in order to determine whether they kill parasites through the release of specific mediators or activate additional cell types in a common pathway of resistance. Efforts will also be made to determine whether the function of malaria- protective cloned T cells can be modulated by T cells displaying antigen-specific suppressive activity.