The role of osteopontin in the generation of memory CD8 T cells during influenza virus infection

适应性免疫系统产生记忆细胞，在二次抗原相遇后诱导快速而强大的免疫反应。记忆CD8^T细胞是抵御感染和癌症的保护性免疫的关键组成部分。因此，了解记忆性CD8^T细胞产生和维持的机制对于诱导有效的记忆性CD8^T细胞反应具有重要意义。最近的研究表明，炎症细胞因子IL-12通过调节转录因子T-bet的表达，促进终末效应T细胞的产生，而不是记忆前体效应T细胞的产生。在这项研究中，我们报道了炎症细胞因子骨桥蛋白(OPN)在流感病毒感染过程中调节记忆CD8T细胞的产生。尽管OPN野生型(OPN WT)和OPN敲除(OPN KO)小鼠具有相似数量的病毒特异性效应CD8^T细胞，但OPN KO小鼠产生的病毒特异性效应CD8^T细胞与OPN WT小鼠相比，T-bet表达水平较低，记忆前体细胞数量增加。这导致OPN KO小鼠的记忆CD8^T细胞数量持续增加。对骨髓来源的树突状细胞(BMDCs)的研究表明，BMDCs的opn缺乏导致了在流感病毒刺激下产生低水平的IL-12。因此，我们推测在病毒感染的急性期，OPN通过调节细胞因子环境来调节记忆前体效应物CD8+T细胞的产生。这一发现可能对OPN在获得性免疫反应中的作用提供新的见解。

The adaptive immune system generates memory cells, which induce a rapid and robust immune response following secondary antigen encounter. Memory CD8^+T cells are a critical component of protective immunity against infections and cancers. Therefore, understanding the mechanism whereby memory CD8^+T cells are generated and maintained is important for inducing effective memory CD8^+T cell response. Recent studies have demonstrated that the inflammatory cytokine IL-12 favors the generation of terminal effector CD8^+T cells rather than memory precursor effector CD8^+T cells by regulating the expression of the transcription factor T-bet. In this study, we report that the inflammatory cytokine osteopontin(Opn) modulates memory CD8^+T cell generation during influenza virus infection. Although Opn-wild-type(Opn WT) and Opn-knockout(Opn KO) mice had similar numbers of virus-specific effector CD8^+T cells, virus-specific effector CD8^+T cells generated in Opn KO mice showed low levels of T-bet expression and an increased memory precursor cell population compared with cells generated in Opn WT mice. This resulted in the persistently increased number of memory CD8^+T cells in Opn KO mice. Studies with bone marrow-derived dendritic cells(BMDCs) demonstrated that Opn-deficiency in BMDCs results in low levels of IL-12 production in response to the stimulation with influenza virus. Thus, we hypothesize that Opn modulates the generation of memory precursor effector CD8^+T cells by regulating cytokine milieu during the acute phase of virus infection. This finding may provide new insight into the role of Opn in adaptive immune response.