T CELL SUBSETS IN CUTANEOUS LEISHMANIASIS

皮肤利什曼病中的 T 细胞亚群

• 批准号: 3142101
• 负责人: JAY P FARRELL
• 金额: $ 26.66万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3142101
• 关键词: CD8 molecule; Leishmania; antigen antibody reaction; athymic mouse; cellular immunity; cellular pathology; cytokine; enzyme linked immunosorbent assay; genetic strain; helper T lymphocyte; immunization; immunoregulation; interferons; laboratory mouse; leishmaniasis; leukocyte activation /transformation; parasitic disease chemotherapy; pathologic process; protozoal antigen; radioimmunoassay; skin infection; tissue /cell culture

Leishmania major infections in (C57BL/6 x BALB/c) Fl mice are either healing or non-healing, depending on the site of parasite inoculation. Thus, lesions in the footpad spontaneously resolve whereas lesions in the dorsal skin at the base of the tail are progressive and ultimately fatal. Based on previous evidence that healing and non-healing infections correlated with the activation of Thl versus Th2 CD4+ cells, site-specific infections in Fl mice will be analyzed to determine mechanisms which may influence the development of divergent patterns of T helper subset activation in the same mouse. Since Fl mice, in contrast to parental strains, develop mixed Thl/Th2 responses during early stages of infection, studies will focus on events which modify Thl vs Th2 induction, as well as events which regulate the divergence of mixed responses toward dominance of a specific subset. Specifically, efforts will be made to determine how host antibody may influence the induction of Thl/Th2 cells as well as regulate established Thl/Th2 responses. A similar role for APC populations in the induction and regulation of Th subsets will be sought. In addition, since macrophage products such as IL-1 and PGE2 have been shown to influence disease progression, studies will determine whether these factors simply promote inflammation, or also influence Th subset activation or expansion. Finally, infections in Fl mice will be utilized to determine whether CD8+ cells are important in the development of acquired resistance to L. major and whether these cells are a significant source of IFN-gamma production during infection.

(C57BL/6 x BALB/c) Fl 小鼠中利什曼原虫的主要感染是 治愈或不治愈，取决于寄生虫的部位 接种。 因此，足垫中的病变会自发消退 而尾部背部皮肤的病变是 进步并最终致命。 根据之前的证据 与激活相关的愈合和非愈合感染 F1小鼠中Th1与Th2 CD4+细胞的比较、位点特异性感染 将进行分析以确定可能影响的机制 T辅助子集激活的不同模式的发展 同一个鼠标。 由于 Fl 小鼠与亲本品系相比，发育出混合型 感染早期阶段的Thl/Th2反应，研究将 关注改变Thl vs Th2诱导的事件以及事件 调节对主导地位的混合反应的分歧 的特定子集。 具体来说，将努力 确定宿主抗体如何影响 Th1/Th2 的诱导 细胞以及调节已建立的 Th1/Th2 反应。 类似的 APC 群体在 Th 诱导和调节中的作用 将寻找子集。 此外，由于巨噬细胞产物如 因为 IL-1 和 PGE2 已被证明可以影响疾病进展， 研究将确定这些因素是否只是促进 炎症，或者也影响 Th 亚群的激活或扩张。 最后，将利用 F1 小鼠的感染来确定是否 CD8+细胞在获得性耐药的发展中很重要 L. Major 以及这些细胞是否是重要来源 感染期间产生 IFN-γ。