CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo.
CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo.
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CD1d 在体外介导 T 细胞依赖性对脑心肌炎病毒 (EMCV) 继发感染的抵抗力，以及在体内对 EMCV 感染的免疫反应。
DOI：
10.1128/jvi.02745-05
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
Exley,MarkA
中科院分区：
文献类型：
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作者：
Ilyinskii,PetrO;Wang,Ruojie;Balk,StevenP;Exley,MarkA
先天性和适应性免疫应答已经进化出用于控制不同病毒病原体的不同策略。脑心肌炎病毒（EMCV）是一种小核糖核酸病毒，可在感染后数天内引起瘫痪、糖尿病和心肌炎。体内针对EMCV的最佳先天免疫应答需要CD 1d。抗原呈递细胞CD 1d与不同的自然杀伤T细胞（“NKT”）群体的相互作用可诱导快速的γ干扰素（IFN-γ）产生和NK细胞活化。进一步在体外和体内研究了CD 1d缺陷小鼠（缺乏所有NKT细胞）对急性EMCV感染的T细胞应答。在体外感染的CD 1d敲除（KO）脾细胞培养物中，EMCV持续处于较高水平。此外，体外对EMCV感染重复周期的最佳抗性也显示依赖于CD 1d。然而，这并没有反映在NK细胞活化的相对水平上，而是反映在CD 4+和CD 8 + T细胞群体的反应上。与野生型相比，体外重复EMCV感染诱导的CD 1d缺陷型脾细胞IFN-γ和α干扰素（IFN-α）较少。此外，通过添加阻断性抗CD 1d抗体，野生型脾细胞中的EMCV复制水平显著且特异性地增加。耗竭实验表明，树突状细胞对抗EMCV应答的贡献小于NK和NKT细胞的组合，并且这些细胞类型都不是IFN-α的主要来源。最后，体内EMCV感染在CD 1d-KO小鼠中产生的病毒血症水平高于野生型动物，同时淋巴细胞活化和IFN-α产生显著减少。这些结果表明，存在一种以前未被认识到的抗病毒适应性细胞免疫应答的快速CD 1d依赖性刺激机制。
The innate and adaptive immune responses have evolved distinct strategies for controlling different viral pathogens. Encephalomyocarditis virus (EMCV) is a picornavirus that can cause paralysis, diabetes, and myocarditis within days of infection. The optimal innate immune response against EMCV in vivo requires CD1d. Interaction of antigen-presenting cell CD1d with distinct natural killer T-cell (“NKT”) populations can induce rapid gamma interferon (IFN-γ) production and NK-cell activation. The T-cell response of CD1d-deficient mice (lacking all NKT cells) against acute EMCV infection was further studied in vitro and in vivo. EMCV persisted at higher levels in CD1d-knockout (KO) splenocyte cultures infected in vitro. Furthermore, optimal resistance to repeat cycles of EMCV infection in vitro was also shown to depend on CD1d. However, this was not reflected in the relative levels of NK-cell activation but rather by the responses of both CD4+and CD8+T-cell populations. Repeated EMCV infection in vitro induced less IFN-γ and alpha interferon (IFN-α) from CD1d-deficient splenocytes than with the wild type. Furthermore, the level of EMCV replication in wild-type splenocytes was markedly and specifically increased by addition of blocking anti-CD1d antibody. Depletion experiments demonstrated that dendritic cells contributed less than the combination of NK and NKT cells to anti-EMCV responses and that none of these cell types was the main source of IFN-α. Finally, EMCV infection in vivo produced higher levels of viremia in CD1d-KO mice than in wild-type animals, coupled with significantly less lymphocyte activation and IFN-α production. These results point to the existence of a previously unrecognized mechanism of rapid CD1d-dependent stimulation of the antiviral adaptive cellular immune response.