Reduction of Antiviral CD8 Lymphocytes In Vivo with Dendritic Cells Expressing Fas Ligand—Increased Survival of Viral (Lymphocytic Choriomeningitis Virus) Central Nervous System Infection1
Reduction of Antiviral CD8 Lymphocytes In Vivo with Dendritic Cells Expressing Fas Ligand—Increased Survival of Viral (Lymphocytic Choriomeningitis Virus) Central Nervous System Infection1
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DOI：
10.4049/jimmunol.169.9.4867
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发表时间：
2002-11
期刊：
影响因子：
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通讯作者：
T. Wolfe;C. Asseman;A. Hughes;H. Matsue;A. Takashima;M. V. von Herrath
中科院分区：
文献类型：
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作者：
T. Wolfe;C. Asseman;A. Hughes;H. Matsue;A. Takashima;M. V. von Herrath
体内给予表达Fas配体的APC（Fas-L+树突状细胞（DC））已显示出抑制过敏反应和移植排斥反应的希望。由于在这些研究中的作用主要是对CD 4淋巴细胞，我们的目标是评估这种杀伤DC消除抗病毒CD 8淋巴细胞的能力，并以这种方式改善病毒免疫病理学，或相反，阻碍病毒清除。静脉注射Fas-L+ DCs导致脑内感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）后裂解性CD 8前体减少50%，因此，LCMV脑膜炎的免疫病理学和存活率得到改善，而病毒清除率不受影响。在转移研究中，Fas-L+ DC的作用仅在经验丰富的而非幼稚的CD 8淋巴细胞上可定量。重要的是，在治疗前用病毒Ag加载Fas-L+ DC对于实现这种效果是不必要的，这表明非LCMV感染的Fas-L+ DC在体内急性LCMV感染期间获得病毒Ag。我们的研究描绘了体内Fas-L+ DCs临床应用的重要方面。人们应该预期，当急性感染正在进行时，它们获得病毒Ag并在一定程度上抑制抗病毒CD 8反应。在安全性方面，感染的消退（至少在LCMV的情况下）不受抑制是令人鼓舞的。
In vivo administration of APC expressing Fas ligand (Fas-L+ dendritic cells (DCs)) has shown promise in dampening allergic reactions and transplant rejection. Since the effect in these studies was mainly on CD4 lymphocytes, our goal was to evaluate the ability of such killer DCs to eliminate antiviral CD8 lymphocytes and in this way ameliorate viral immunopathology or, conversely, impede viral clearance. Intravenous administration of Fas-L+ DCs resulted in a 50% reduction of lytic CD8 precursors following intracerebral infection with lymphocytic choriomeningitis virus (LCMV), and accordingly, immunopathology and survival of LCMV meningitis were improved, whereas viral clearance remained unaffected. In transfer studies the effect of the Fas-L+ DCs was only quantifiable on experienced, not naive, CD8 lymphocytes. Importantly, loading of Fas-L+ DCs with viral Ag before therapy was not necessary to achieve this effect, indicating that non-LCMV-infected Fas-L+ DCs acquired viral Ag during acute LCMV infection in vivo. Our studies delineate important aspects for the clinical use of Fas-L+ DCs in vivo. One should expect that they acquire viral Ags and suppress antiviral CD8 responses to some degree when given while an acute infection is ongoing. In terms of safety it is encouraging that resolution of the infection, at least in the case of LCMV, is not inhibited.