用墨西哥利什曼原虫LPG疫苗接种诱导CD8 +中的PD-1和巨噬细胞中的PD-L2，从而抑制免疫应答：评估疫苗效力的模型
Vaccination with Leishmania mexicana LPG induces PD-1 in CD8+ and PD-L2 in macrophages thereby suppressing the immune response: A model to assess vaccine efficacy
摘要：
利什曼原虫脂磷酸聚糖是一种已被用作候选疫苗的分子，但结果相互矛盾。由于保护作用的失败可能与T细胞反应的抑制有关，因此我们分析了不同剂量的墨西哥利什曼原虫LPG免疫BALB/c小鼠并在体外用不同浓度的LPG再刺激的情况下，CD 8+和CD 4+淋巴细胞中抑制性受体PD-1及其配体PD-L2的表达。用LPG接种增强了CD 8+细胞中PD-1的表达。活化分子CD 137在来自接种疫苗的小鼠的CD 8+细胞中减少。体外再刺激以剂量依赖性方式增强健康小鼠巨噬细胞中的PD-L2表达。PD-1、PD-L2和CD 137的表达根据免疫和体外再刺激期间使用的LPG的量进行调节。我们分析了这些分子在感染1 × 10 - 4或1 × 10 - 5 L的小鼠中的表达。mexicana前鞭毛体，并在体外用LPG再刺激。用1 × 10 - 5寄生虫感染增加了CD 8+中的PD-1表达，并减少了巨噬细胞中的PD-L2。当这些CD 8+细胞在体外用LPG再刺激时，模拟第二次暴露于寄生虫抗原，PD-1表达以剂量依赖性方式显著增加。我们得出结论，CD 8 + T淋巴细胞和巨噬细胞表达抑制分子根据利什曼原虫LPG的浓度和寄生虫负荷。用增加量的LPG接种或用较高寄生虫数量感染诱导PD-1的表达增强和CD 8+细胞的功能失活，这可能在利什曼病中具有关键后果，因为这些细胞对于疾病控制至关重要。
英文摘要：
Leishmania lipophosphoglycan is a molecule that has been used as a vaccine candidate, with contradictory results. Since unsuccessful protection could be related to suppressed T cell responses, we analyzed the expression of inhibitory receptor PD-1 in CD8+ and CD4+ lymphocytes and it is ligand PD-L2 in macrophages of BALB/c mice immunized with various doses of Leishmania mexicana LPG and re-stimulated in vitro with different concentrations of LPG. Vaccination with LPG enhanced the expression of PD-1 in CD8+ cells. Activation molecules CD137 were reduced in CD8+ cells from vaccinated mice. In vitro re-stimulation enhanced PD-L2 expression in macrophages of healthy mice in a dose-dependent fashion. The expression of PD-1, PD-L2, and CD137 is modulated according to the amount of LPG used during immunization and in vitro re-stimulation. We analyzed the expression of these molecules in mice infected with 1 x 10'4 or 1 x 10'5 L. mexicana promastigotes and re-stimulated in vitro with LPG. Infection with 1 x 10'5 parasites increased the PD-1 expression in CD8+ and diminished PD-L2 in macrophages. When these CD8+ cells were re-stimulated in vitro with LPG, simulating a second exposure to parasite antigens, PD-1 expression increased significantly more, in a dose-dependent fashion. We conclude that CD8+ T lymphocytes and macrophages express inhibition molecules according to the concentrations of Leishmania LPG and to the parasite load. Vaccination with increased amounts of LPG or infections with higher parasite numbers induces enhanced expression of PD-1 and functional inactivation of CD8+ cells, which can have critical consequences in leishmaniasis since these cells are crucial for disease control.
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