Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.
Dev Comp Immunol. 2011 May;35(5):620-7. doi: 10.1016/j.dci.2011.01.007. Epub 2011 Jan 15.
Infectious bursal disease (IBD) is an economically important immunosuppressive disease of chickens. The IBD virus (IBDV) actively replicates in B cells and causes severe bursal damage. Generally, T cells are refractory to infection with IBDV but are known to promote virus clearance. However, the mechanisms of T cell mediated viral clearance are not well understood. In this study, we evaluated the molecular mechanisms of cytotoxic T cell responses in the pathogenesis of IBD in chickens. Infection of chickens with IBDV was accompanied by the infiltration of CD4(+) and CD8(+) T cells in the bursa. There was an upregulation in the gene expression of important cytolytic molecules; perforin (PFN), granzyme-A (Gzm-A), DNA repair and apoptotic proteins; high mobility proteins group (HMG) and poly (ADP-ribose) polymerase (PARP) in the bursa of Fabricius (BF) whereas expression of NK (natural killer) lysin was downregulated. Importantly, PFN producing CD4(+) and CD8(+) T cells were also detected in the bursa of IBDV-infected chickens by immunohistochemistry. The Th1 cytokines, IL-2 and IFN-γ expression was also strongly upregulated, suggesting the activation of T cells. The findings of this study highlight the mechanisms of IBD pathogenesis and the role of cytotoxic T cells in the clearance of virus-infected cells.
传染性囊病(IBD)是一种对鸡具有重要经济意义的免疫抑制性疾病。IBD 病毒(IBDV)在 B 细胞中积极复制,导致严重的法氏囊损伤。通常,T 细胞不易感染 IBDV,但已知可促进病毒清除。然而,T 细胞介导的病毒清除机制尚不清楚。在这项研究中,我们评估了鸡传染性囊病发病机制中细胞毒性 T 细胞反应的分子机制。鸡感染 IBDV 后,CD4(+)和 CD8(+)T 细胞浸润法氏囊。法氏囊中重要细胞溶解分子的基因表达上调;穿孔素(PFN)、颗粒酶-A(Gzm-A)、DNA 修复和凋亡蛋白;高迁移率蛋白组(HMG)和多聚(ADP-核糖)聚合酶(PARP),而 NK(自然杀伤)溶素的表达下调。重要的是,通过免疫组织化学也在 IBDV 感染鸡的法氏囊中检测到产生 PFN 的 CD4(+)和 CD8(+)T 细胞。Th1 细胞因子,IL-2 和 IFN-γ 的表达也被强烈上调,表明 T 细胞被激活。这项研究的结果强调了 IBD 发病机制的机制以及细胞毒性 T 细胞在清除病毒感染细胞中的作用。