Characterization of myeloid suppressor cell activity in experimental leishmaniasis

在实验性利什曼病中，疾病的临床过程取决于受感染小鼠品系的遗传决定的能力，以产生保护性T细胞介导的免疫应答。C57BL/6小鼠控制寄生虫复制，而BALB/c小鼠发展慢性病程。考虑到这些不同的表型，最有可能的是调节针对L. C57 BL/6和BALB/c小鼠的主要寄生虫不同。最近，骨髓抑制细胞已被描述为抑制T细胞功能。最有效的抑制细胞是炎性CD11b+单核细胞（IMC），其特征在于高水平的淋巴细胞抗原6复合物C（Ly-6C）表达，但Ly-6G阴性。我们定量了感染C57 BL/6和BALB/c小鼠的感染部位和皮肤引流淋巴结（SDLN）处的IMC。BALB/c小鼠感染部位和SDLN的IMC增加，而C57 BL/6 SDLN中的IMC数量不受影响。因此，我们提出了一个假设，即IMC迁移到感染部位和BALB/c小鼠的SDLN，以抑制有效的T细胞反应的发展。本项目的总体目标是描述在利什曼病实验模型中由IMC介导的不同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.