NKT Cell-Plasmacytoid Dendritic Cell Cooperation via OX40 Controls Viral Infection in a Tissue-Specific Manner
NKT Cell-Plasmacytoid Dendritic Cell Cooperation via OX40 Controls Viral Infection in a Tissue-Specific Manner
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DOI：
10.1016/j.immuni.2008.12.017
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发表时间：
2009-02-20
期刊：
影响因子：
32.4
通讯作者：
Lehuen, Agnes
中科院分区：
文献类型：
--
作者：
Diana, Julien;Griseri, Thibault;Lehuen, Agnes
不变的自然杀伤T（iNKT）细胞促进对各种病原体的免疫反应，但iNKT细胞如何控制抗病毒反应尚不清楚。在这里，我们发现iNKT细胞在淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染的小鼠中诱导组织特异性抗病毒作用。事实上，iNKT细胞抑制胰腺和肝脏中的病毒复制，但不抑制脾脏中的病毒复制。在胰腺中，iNKT细胞表达OX 40分子并通过OX 40-OX 40配体相互作用促进浆细胞样树突状细胞（pDC）产生I型干扰素（IFN）。随后，这种iNKT细胞-pDC合作减弱了胰腺中的抗病毒适应性免疫应答，但不减弱脾脏中的抗病毒适应性免疫应答。胰腺抗LCMV CD 8（+）T细胞反应的减弱防止了在胰岛β细胞中表达LCMV蛋白的转基因小鼠的组织损伤。因此，本研究确定pDC作为iNKT细胞的重要伙伴，用于在外周组织中建立有效、无害的抗病毒应答。
Invariant natural killer T (iNKT) cells promote immune responses to various pathogens, but exactly how iNKT cells control antiviral responses is unclear. Here, we showed that iNKT cells induced tissue-specific antiviral effects in mice infected by lymphocytic choriomeningitis virus (LCMV). Indeed, iNKT cells inhibited viral replication in the pancreas and liver but not in the spleen. In the pancreas, iNKT cells expressed the OX40 molecule and promoted type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) through OX40-OX40 ligand interaction. Subsequently, this iNKT cell-pDC cooperation attenuated the antiviral adaptive immune response in the pancreas but not in the spleen. The dampening of pancreatic anti-LCMV CD8(+) T cell response prevented tissue damage in transgenic mice expressing LCMV protein in islet beta cells. Thus, this study identifies pDCs as an essential partner of iNKT cells for mounting an efficient, nondeleterious antiviral response in peripheral tissue.