Characterization of myeloid suppressor cell activity in experimental leishmaniasis

在实验性利什曼病中，临床病程取决于感染小鼠品系的遗传决定能力，即启动保护性T细胞介导的免疫反应的能力。C57BL/6小鼠控制寄生虫复制，而BALB/c小鼠发展为慢性病程。考虑到这些不同的表型，很可能C57BL/6和BALB/c小鼠对主要寄生虫的适应性免疫反应的调节参数不同。最近，髓系抑制细胞被描述为抑制T细胞功能。最有效的抑制细胞是炎性CD11b+单核细胞(IMC)，其特征是高水平表达淋巴细胞抗原6复合体C(Ly-6C)，但不表达Ly-6G。我们对感染C57BL/6和BALB/c小鼠的感染部位和皮肤引流淋巴结(SDLN)处的IMC进行了定量。BALB/c小鼠感染部位和SDLN的IMC数量增加，而C57BL/6 SDLN的IMC数量不受影响。因此，我们提出了一种假设，即IMCs迁移到BALB/c小鼠的感染部位和SDLN，以抑制高效T细胞反应的发展。这个项目的总体目标是在利什曼病的实验模型中表征IMCs介导的不同的T细胞抑制机制。

In experimental leishmaniasis, the clinical course of disease depends on the genetically determined ability of the infected mouse strain to mount a protective T cell-mediated immune response. C57BL/6 mice control parasite replication, whereas BALB/c mice develop a chronic course of disease. Considering these divergent phenotypes, it is most likely that parameters regulating the adaptive immune response against L. major parasites differ in C57BL/6 and BALB/c mice. Recently, myeloid suppressor cells have been described to suppress T cell functions. The most potent suppressive cells are inflammatory CD11b+ monocytes (IMC) that are characterized by the expression of high levels of lymphocyte antigen 6 complex C (Ly-6C), but are negative for Ly-6G. We quantified IMCs at the site of infection and skin-draining lymph nodes (SDLNs) of infected C57BL/6 and BALB/c mice. BALB/c mice showed an increase of IMC at the site of infection and SDLNs, whereas the numbers of IMCs in C57BL/6 SDLNs were not affected. Thus, we propose the hypothesis that IMCs migrate to the site of infection and SDLNs of BALB/c mice to suppress the development of an efficient T cell response. The overall goal of this project is to characterize the different T cell-suppressing mechanisms mediated by IMCs in the experimental model of leishmaniasis.