PD-L2+dendritic cells and PD-1+CD4+T cells in schistosomiasis correlate with morbidity
PD-L2+dendritic cells and PD-1+CD4+T cells in schistosomiasis correlate with morbidity
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DOI：
10.1111/j.1365-3024.2005.00742.x
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发表时间：
2005-01-01
影响因子：
2.2
通讯作者：
Reed, AM
中科院分区：
文献类型：
--
作者：
Colley, DG;Sasser, LE;Reed, AM
树突状细胞（DC）是诱导和控制免疫反应的关键抗原递呈细胞。PD-L2（B7-DC）是DC亚群上的调节配体，并与存在于一些活化的T淋巴细胞上的共调节受体PD-1结合，导致下调。我们现在发现，在实验性血吸虫病的早期（5周），脾脏CD 11 c +/B220- DC表达PD-L2的比例显著较高，感染后6周，脾脏CD 4 T细胞表达PD-1的比例较高。在该CBA/J小鼠/曼氏血吸虫慢性感染模型中，我们已经表明大多数小鼠发展为中度发病率（中度脾肿大综合征，MSS），而一些平行感染的小鼠表达不同的免疫特征并死亡或发展为重度发病率（脾肿大综合征，HSS）。我们现在报告了表达PD-L2的脾脏CD 11 c +/B220- DC的比例与MSS的表现之间的正相关性。相反，表达PD-1的脾脏CD 3 +/CD 4 + T淋巴细胞比例与MSS呈负相关。数据表明，脂质体可诱导表达PD-L2的B220阴性DC的百分比持续升高。此外，当这种潜在的免疫调节环境长期发生时，受感染的小鼠最有可能发展为MSS，表现出中度发病率。
Dendritic cells (DC) are critical antigen-presenting cells for the induction and control of immune responses. PD-L2 (B7-DC) is a regulatory ligand on subpopulations of DC, and binds to the co-regulatory receptor PD-1, present on some activated T lymphocytes, leading to down-regulation. We now show that very early during experimental schistosomiasis (by 5 weeks) a significantly higher proportion of splenic CD11c+/B220- DC express PD-L2, and by 6 weeks after infection a higher proportion of splenic CD4 T cells express PD-1. In this CBA/J mouse/Schistosoma mansoni chronic infection model we have shown that most mice develop moderate morbidity (Moderate Splenomegaly Syndrome, MSS), while some parallel-infected mice express different immune characteristics and die or develop severe morbidity (Hypersplenomegaly Syndrome, HSS). We now report a positive correlation between the proportion of splenic CD11c+/B220- DC that express PD-L2 and showing MSS. In contrast, there is an inverse correlation between the proportion of splenic CD3+/CD4+ T lymphocytes that express PD-1 and showing MSS. The data demonstrate that schistosomes can induce sustained elevated percentages of PD-L2-expressing, B220-negative DC. Furthermore, when this potentially immunoregulatory environment occurs chronically, infected mice are most likely to have developed MSS, expressing moderate morbidity.