OX40参与RSV气道炎症反应中CD4^+T细胞的增殖活化

Participation of OX40 in Proliferation and Activation of CD4^+T Cells in RSV-Induced Airway Inflammation

OX40是TNFR超家族成员之一,主要表达于活化的CD4^+T细胞表面。OX40能促进CD4+T细胞的增殖与活化,但其在呼吸道合胞病毒(respiratory syncytial virus,RSV)感染所诱发的气道炎症反应中对CD4^+T细胞增殖与活化的作用尚不十分清楚。通过建立RSV急性感染的实验动物模型,采用流式细胞术、免疫磁珠分选、Real-timeRT-PCR、Elisa、WesternBlot等实验方法,旨在揭示在RSV感染性气道炎症中OX40对CD4^+T细胞增殖与活化的影响作用。结果显示,RSV感染后脾组织内表达OX40的CD4^+T细胞数量及CD4^+T细胞OX40mRNAs和OX40蛋白表达水平显著增加。从感染3d的BALB/c鼠脾组织分选CD4^+T细胞进行体外培养并加入OX40激动型抗体,发现加入OX40激动型抗体的CD4^+T细胞组与未加组相比,其细胞因子IL-2、IFN-γ和IL-13的表达水平显著增高。证实在感染性气道炎症中OX40对CD4^+T的细胞增殖与活化起着重要的调控作用。

OX40 is one member of the TNFR ( tumor necrosis factor receptor) superfamily and mainly expressed on the surface of activated CD4^+ T cells. OX40 can promote the proliferation and activation of CD4^+ T cells. However, the effect of OX40 on the proliferation and activation of CD4^+ T cells during RSV-induced airway inflammation remains not very clear. In this study,animal models with acute RSV ( respiratory syncytial virus) infection was established, and adopted the methods of flow cytometry,immuno-magnetic separation,real-time RT-PCR,ELISA and Western Blot to reveal the role of OX40 on the proliferation and activation of CD4^+ T cells during RSV-infected airway inflam- mation. The results showed that RSV infection significantly enhanced the number of OX40^+ CD4^+ T cells as well as the expression of OX40 mRNAs and OX40 protein within splenic CD4^+ T cells. In vitro study,CD4^+ T cells were iso- lated from the spleens of BALB/c mice 3 days after RSV infection and cultured alone or together with agonist anti- OX40 for 24 hours. As expected,the cytokines expression of IL-2,IFN-γ and IL-13 in CD4^+ T cells were clearly en- hanced when cultured with agonist anti-OX40 as compared to that when cultured alone. The results indicated-that OX40 played an important role in the proliferation and activation of CD4^+ T cells in RSV-induced airway inflammation.