Complement-dependent enhancement of CD8+ T cell immunity to lymphocytic choriomeningitis virus infection in decay-accelerating factor-deficient mice
Complement-dependent enhancement of CD8+ T cell immunity to lymphocytic choriomeningitis virus infection in decay-accelerating factor-deficient mice
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DOI：
10.4049/jimmunol.179.5.3178
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发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Song, Wen-Chao
中科院分区：
文献类型：
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作者：
Fang, Chongyun;Miwa, Takashi;Song, Wen-Chao
衰变加速因子（DAF，CD55）是一种糖基磷脂酰肌醇（GPI）锚定的膜蛋白，它调节自身细胞上的补体激活。除了保护宿主组织免受补体攻击外，在模型抗原免疫的情况下，DAF已被证明可抑制CD4(+) T细胞免疫。然而，在病原体感染期间DAF是否调节天然T细胞免疫应答尚不清楚。在本研究中，我们描述了DAF对淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染的CD8(+) T细胞应答具有显著的调节作用。与野生型小鼠相比，DAF基因敲除（Daf -1 -1 -）小鼠在急性或慢性LCMV感染后，脾脏中总的以及病毒抗原特异性CD8(+) T细胞的扩增显著增加。来自LCMV感染的Daf -1 -1 -小鼠的脾细胞对负载病毒抗原的靶细胞也显示出比野生型小鼠的细胞显著更高的杀伤活性，并且Daf -1 (-/-)小鼠更有效地清除LCMV。重要的是，从Daf -1 -1 -小鼠中缺失补体蛋白C3或过敏毒素C5a的受体（C5aR）可逆转增强的CD8(+) T细胞免疫表型。这些结果表明，DAF是病毒感染中CD8(+) T细胞免疫的重要调节因子，并且它通过作为补体抑制剂来防止病毒触发的补体激活和C5aR信号传导而发挥这一作用。DAF在病毒感染中的这种作用模式与CD59不同，并表明GPI锚定的膜补体抑制剂可通过补体依赖或非依赖机制调节对病毒感染的T细胞免疫。
Decay-accelerating factor (DAF, CD55) is a GPI-anchored membrane protein that regulates complement activation on autologous cells. In addition to protecting host tissues from complement attack, DAF has been shown to inhibit CD4(+) T cell immunity in the setting of model Ag immunization. However, whether DAF regulates natural T cell immune response during pathogenic infection is not known. We describe in this study a striking regulatory effect of DAF on the CD8(+) T cell response to lymphocytic choriomeningitis virus (LCMV) infection. Compared with wild-type mice, DAF knockout (Daf-1-1-) mice had markedly increased expansion in the spleen of total and viral Ag-specific CD8(+) T cells after acute or chronic LCMV infection. Splenocytes from LCMV-infected Daf-1-1- mice also displayed significantly higher killing activity than cells from wild-type mice toward viral Ag-loaded target cells, and Daf- 1 (-/-) mice cleared LCMV more efficiently. Importantly, deletion of the complement protein C3 or the receptor for the anaphylatoxin C5a (C5aR) from Daf-1-1- mice reversed the enhanced CD8' T cell immunity phenotype. These results demonstrate that DAF is an important regulator of CD8' T cell immunity in viral infection and that it fulfills this role by acting as a complement inhibitor to prevent virus-triggered complement activation and C5aR signaling. This mode of action of DAF contrasts with that of CD59 in viral infection and suggests that GPI-anchored membrane complement inhibitors can regulate T cell immunity to viral infection via either a complement-dependent or -independent mechanism.