Critical Role of an MHC Class I-Like/Innate-Like T Cell Immune Surveillance System in Host Defense against Ranavirus (Frog Virus 3) Infection
Critical Role of an MHC Class I-Like/Innate-Like T Cell Immune Surveillance System in Host Defense against Ranavirus (Frog Virus 3) Infection
复制标题
DOI：
10.3390/v11040330
复制
发表时间：
2019-04-01
期刊：
影响因子：
4.7
通讯作者：
Robert, Jacques
中科院分区：
文献类型：
--
作者：
Edholm, Eva-Stina Isabella;Andino, Francisco De Jesus;Robert, Jacques
除了经典的主要组织相容性复合体（MHC）Ia类限制性的常规分化簇8（CD8）T细胞在抗病毒宿主免疫应答中的中心作用外，两栖动物非洲爪蟾还严重依赖MHC I类（mhc1b10.1.L或XNC10）限制性的先天性（i）样T细胞（iV6 T细胞）来控制蛙病毒3（FV3）的感染。为了补充和扩展我们先前的反向遗传研究，表明iV6 T细胞是蝌蚪存活以及及时有效的成人病毒清除所必需的，我们检查了iV6 T细胞对FV3应答的条件和动力学。使用FV3敲除（KO）生长缺陷突变体，我们发现XNC10限制性I类基因的上调和iV6 T细胞的快速募集依赖于可检测的病毒复制和生产性FV3感染。此外，通过用XNC10四聚体体内耗竭，我们证明了iV6 T细胞的直接抗病毒效应子功能。值得注意的是，短暂的iV6 T细胞缺陷延迟了先天性干扰素和细胞因子基因应答，导致长期的阴性不能控制FV3感染。这些发现表明，在非洲爪蟾和其他两栖动物中，基于非多态性MHC I类分子早期激活iT细胞的免疫监视系统对于有效的抗病毒免疫应答是重要的。
Besides the central role of classical Major Histocompatibility Complex (MHC) class Ia-restricted conventional Cluster of Differentiation 8 (CD8) T cells in antiviral host immune response, the amphibian Xenopus laevis critically rely on MHC class I-like (mhc1b10.1.L or XNC10)-restricted innate-like (i)T cells (iV6 T cells) to control infection by the ranavirus Frog virus 3 (FV3). To complement and extend our previous reverse genetic studies showing that iV6 T cells are required for tadpole survival, as well as for timely and effective adult viral clearance, we examined the conditions and kinetics of iV6 T cell response against FV3. Using a FV3 knock-out (KO) growth-defective mutant, we found that upregulation of the XNC10 restricting class I-like gene and the rapid recruitment of iV6 T cells depend on detectable viral replication and productive FV3 infection. In addition, by in vivo depletion with XNC10 tetramers, we demonstrated the direct antiviral effector function of iV6 T cells. Notably, the transitory iV6 T cell defect delayed innate interferon and cytokine gene response, resulting in long-lasting negative inability to control FV3 infection. These findings suggest that in Xenopus and likely other amphibians, an immune surveillance system based on the early activation of iT cells by non-polymorphic MHC class-I like molecules is important for efficient antiviral immune response.