A Complementary Role for the Tetraspanins CD37 and Tssc6 in Cellular Immunity
A Complementary Role for the Tetraspanins CD37 and Tssc6 in Cellular Immunity
复制标题
DOI：
10.4049/jimmunol.0902867
复制
发表时间：
2010-09-15
影响因子：
4.4
通讯作者：
Wright, Mark D.
中科院分区：
文献类型：
--
作者：
Gartlan, Kate H.;Belz, Gabrielle T.;Wright, Mark D.
四跨膜蛋白-四跨膜蛋白相互作用在膜组织中的合作性质表明功能重叠在四跨膜蛋白生物学中可能是重要的。先前对四跨膜蛋白CD 37和Tssc 6在免疫系统中的功能研究发现，CD 37和Tssc 6都在体外调节T细胞增殖反应。CD 37（-/-）小鼠也表现出过度刺激的树突状细胞表型和失调的体液反应。在这项研究中，我们描述了为研究这些四跨膜蛋白之间的功能重叠而产生的“双敲除”小鼠（CD 37（-/-）Tssc 6（-/-））的特征。在细胞免疫中鉴定了这两种蛋白质的协同作用的强有力证据，其中与单一敲除对应物相比，CD 37（-/-）Tssc 6（-/-）小鼠中的体外T细胞增殖应答和树突状细胞刺激能力均显著夸大。尽管在体外有这些夸大的细胞反应，但CD 37（-/-）Tssc 6（-/-）小鼠对自身免疫诱导并不更敏感。然而，在CD 37（-/-）Tssc 6（-/-）小鼠中对病原体的体内应答似乎较差，其显示出产生流感特异性T细胞的能力降低，并且当感染约氏疟原虫时显示出快速发作的高寄生虫血症。因此，在不存在CD 37和Tssc 6的情况下，与CD 37（-/-）或Tssc 6（-/-）小鼠相比，免疫功能进一步改变，表明这两种分子在细胞免疫中的互补作用。免疫学杂志，2010，185：3158-3166。
The cooperative nature of tetraspanin-tetraspanin interactions in membrane organization suggests functional overlap is likely to be important in tetraspanin biology. Previous functional studies of the tetraspanins CD37 and Tssc6 in the immune system found that both CD37 and Tssc6 regulate T cell proliferative responses in vitro. CD37(-/-) mice also displayed a hyper-stimulatory dendritic cell phenotype and dysregulated humoral responses. In this study, we characterize "double knockout" mice (CD37(-/-) Tssc6(-/-)) generated to investigate functional overlap between these tetraspanins. Strong evidence for a cooperative role for these two proteins was identified in cellular immunity, where both in vitro T cell proliferative responses and dendritic cell stimulation capacity are significantly exaggerated in CD37(-/-) Tssc6(-/-) mice when compared with single knockout counterparts. Despite these exaggerated cellular responses in vitro, CD37(-/-) Tssc6(-/-) mice are not more susceptible to autoimmune induction. However, in vivo responses to pathogens appear poor in CD37(-/-) Tssc6(-/-) mice, which showed a reduced ability to produce influenza-specific T cells and displayed a rapid onset hyper-parasitemia when infected with Plasmodium yoelii. Therefore, in the absence of both CD37 and Tssc6, immune function is further altered when compared with CD37(-/-) or Tssc6(-/-) mice, demonstrating a complementary role for these two molecules in cellular immunity. The Journal of Immunology, 2010, 185: 3158-3166.