Treg细胞参与LIGHT缺失小鼠对利什曼原虫感染的敏感性

Treg cells involve in LIGHT deficiency-induced susceptibility to Leishmania major infection

目的探讨LIGHT对利什曼原虫(L.major)感染模型中CD4+T细胞亚群免疫应答的影响。方法采用LIGHT KO和野生型(WT)小鼠,经小鼠脚掌注射L.major建立感染模型。从感染第2周至24周连续观察被感染脚掌的病损程度,并测定感染24周小鼠体内寄生虫载量。其次,取感染第7天小鼠引流淋巴结(d LN)细胞,运用3H-Td R掺入方法检测T细胞体外刺激的增殖情况,并且利用ELSIA检测体外刺激后d LN细胞IL-12和IFN-γ的表达水平。最后,通过流式细胞术检测感染第7天小鼠脾脏和d LN中Treg水平。结果 LIGHT KO小鼠被感染脚掌和d LN的寄生虫载量均显著高于WT对照小鼠。感染早期LIGHTKO小鼠d LN中T细胞增殖水平,以及IL-12和IFN-γ的表达水平均显著低于WT对照小鼠。感染早期LIGHT KO小鼠中脾脏和d LN中的Treg细胞百分率相对WT小鼠均显著升高。结论 LIGHT可能通过抑制Treg细胞的产生,促进Th1细胞的分化,从而增强小鼠抗L.major感染的能力。

Helper T cell subsets play a very important role in the resistance or susceptibility to infection of Leishmania major （L.major）. Though there were reports finding that LIGHT can influence Thl response after L.major infection, the role of LIGHT in regulating helper T cell subsets in L. major infection model are not fully understood. In this report, we aimed to investigate the effect of LIGHT on CD4＋ cell responds in L.major infection model. L.major was injected to footpad of mice to build an infection model. Then we found that LIGHT KO mice had more severe Lesions of footpad than WT （wide type） mice, and parasites burden in footpad and draining lymphonode （dLN） in LIGHT KO mice were much more than those of WT mice at 24 weeks post infection. When dLN of mice at 7 days post infection were isolated and stimulated in vitro, T ceils from LIGHT KO mice showed lower proliferation than WT mice, and IL-12 and IFN-γ expressions of the dLN cells from LIGHT KO mice also were lower than that from WT mice. Moreover, we found that the percentage of Treg in spleen and dLN from LIGHT KO mice at 7 days post infection were both higher than those from WT mice. These results suggested that increased Treg in LIGHT KO mice could reduce Thl response, which results in increase of susceptibility to L.major. Thus, LIGHT may enhance resistance to Leishmania major through reducing the Treg expression.