Immunological modulation and control of infections diseases by cytokaines

为了解细胞因子在抗牛白血病病毒(BLV)感染的保护性免疫反应中的作用，对12只绵羊接种BLV后外周血单个核细胞(PBMC)细胞因子基因表达水平进行了分析。所有绵羊感染BLV后，PBMC中干扰素γ、IL 2、IL 4和IL 10mRNA的表达均下调。然而，肿瘤坏死因子α的表达仅在消除了细小病毒的抗病绵羊中上调，而在繁殖细小病毒的易感绵羊中表达下调。提示肿瘤坏死因子α在BLV感染的早期保护中起重要作用。此外，还研究了BLV抗性和易感绵羊PBMC中肿瘤坏死因子受体I型(TNFRI)和II型受体(TNFRIImRNA)的表达。有趣的是，只有在BLV易感的绵羊中α受体的表达显著下调。用肿瘤坏死因子α体外刺激，BLV敏感绵羊PBMC的刺激指数高于BLV抗性绵羊。此外，流式细胞仪分析表明，BLV易感绵羊PBMC上膜形式的肿瘤坏死因子α的表达高于耐药绵羊PBMC，而肿瘤坏死因子DNA被认为是诱导B细胞活化的配体之一。以上结果提示，肿瘤坏死因子α及其受体参与了BLV诱导的绵羊B细胞增殖过程。

In order to understand the role of cytokines in protective immune responses against bovine leukemia virus (BLV) infection, 12 sheep were inoculated with BLV and the levels of cytokine mRNA expressions in the peripheral blood mononuclear cells (PBMCs) were analyzed. The mRNA expressions of IFN γ, IL2, IL4 and IL10 in PBMCs were downregulated after BLV infection in all sheep. However, the expressions of tumor necrosis factor α (TNF α) mRNA was up-regulated only in BLV-resistant sheep in which BLV were eliminated, though down-regulated in -susceptible sheep in which BLV propagated. This may suggest that TNF α play an important role in the protection against BLV infection during the early phase of infection. Additionally, the mRNA expressions of TNF α receptors type I(TNFR I) and type II (TNFR II) were investigated in BLV-resistant and -susceptible sheep PBMCs.Interestingly, the mRNA expression of TNFR I was significantly downregulated only in the BLV-susceptible sheep. By the use of in vitro stimulation with TNF α, higher stimulation index was observed for PBMCs from BLV-susceptible than -resistant sheep. In addition, flowcytometric analysis showed that membrane form of TNF α, which is thought to be one of the ligands which induce B-cell activation, was expressed more on PBMCs from BLV-susceptible than those from -resistant sheep. These results suggest that TNFα and its receptors are involved in the development of BLV-induced B-cell proliferation in sheep.