Requirement for the lymphocyte semaphorin, CD100, in the induction of antigen-specific T cells and the maturation of dendritic cells
Requirement for the lymphocyte semaphorin, CD100, in the induction of antigen-specific T cells and the maturation of dendritic cells
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DOI：
10.4049/jimmunol.169.3.1175
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发表时间：
2002-08-01
影响因子：
4.4
通讯作者：
Kikutani, H
中科院分区：
文献类型：
--
作者：
Kumanogoh, A;Suzuki, K;Kikutani, H
CD100属于信号蛋白家族，其中几个成员在神经元发育过程中扮演排斥性轴突引导因子的角色。我们之前已经证明CD100在不道德免疫中起着至关重要的作用。在这项研究中，我们发现CD100通过树突状细胞（dc）的成熟对细胞免疫也很重要。CD100（-/-）小鼠不能发生髓鞘少突胶质细胞糖蛋白肽诱导的实验性自身免疫性脑脊髓炎，因为在缺乏CD100的情况下，髓鞘少突胶质细胞糖蛋白特异性T细胞不能产生。对OVA特异性tcr转基因小鼠T细胞的体外研究表明，在apc和OVA肽存在的情况下，缺乏CD100的ag特异性T细胞不能分化为产生IL-4或ifn - γ的细胞。此外，来自CD100（-/-）小鼠的dc表现出较差的同种刺激能力，并且在共刺激分子表达和IL-12产生方面存在缺陷。外生的加入；可溶性rCD100可恢复CD100(-/-) dc的正常功能，并进一步增强正常dc的功能。此外，在免疫前用可溶性CD100和抗cd40处理银脉冲dc可显著提高其免疫原性。这种治疗在体内引发了改善的T细胞启动，增强了原发性和记忆性T细胞反应。综上所述，这些结果表明，促进dc成熟的CD100在ag特异性T细胞的激活和分化中是必不可少的。
CD100 belongs to the semaphorin family, several members of which are known to act as repulsive axonal guidance factors during neuronal development. We have previously demonstrated that CD100 plays a crucial role in Immoral immunity. In this study, we show that CD100 is also important for cellular immunity through the maturation of dendritic cells (DCs). CD100(-/-) mice fail to develop experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein peptide, because myelin oligodendrocyte glycoprotein-specific T cells are not generated in the absence of CD100. In vitro studies with T cells from OVA-specific TCR-transgenic mice demonstrate that Ag-specific T cells lacking CD100 fail to differentiate into cells producing either IL-4 or IFN-gamma in the presence of APCs and OVA peptide. In addition, DCs from CD100(-/-) mice display poor allostimulatory capabilities and defects in costimulatory molecule expression and IL-12 production. The addition of exogenous; soluble rCD100 restores normal functions in CD100(-/-) DCs and further enhances functions of normal DCs. Furthermore, treatment of Ag-pulsed DCs with both soluble CD100 and anti-CD40 before immunization significantly enhances their immunogenicity. This treatment elicits improved T cell priming in vivo, enhancing both primary and memory T cell responses. Collectively, these results demonstrate that CD100, which enhances the maturation of DCs, is essential in the activation and differentiation of Ag-specific T cells.