Role of T cells in recovery from bluetongue virus infection in calves

蓝舌病（Bluetongue，BT）是由蓝舌病病毒（Bluetongue virus，BTV）引起的绵羊、牛、山羊和鹿的一种重要传染病。感染BTV的动物会出现发热、嘴唇、口腔、鼻腔和眼睑发红和肿胀，迅速失去健康，肌肉退化和跛行，并可能死于这种疾病。BTV至少有24种不同类型，直到最近，这种疾病主要局限于非洲，亚洲，美洲和澳大利亚的地区。然而，由于气候变化和欧洲天气变暖，BTV感染的蠓传播到南欧，2006年在一些北方欧洲国家爆发了蓝舌病。这是第一次在北方欧洲发现BTV，2007年8月，该病毒传播到英国。在2007年底/2008年初，BTV血清型1抵达法国南部，其分布与BTV-8重叠。这增加了这些病毒株交换基因的可能性。这可能会增强BTV-1混合后代毒株向北传播的能力，并增加北方欧洲和英国第二血清型（BTV-1）的威胁。2008年期间，在荷兰和德国发现了第三种病毒株BTV-6。最近受感染的国家采取的控制措施包括限制动物移动，这会产生重大的经济影响，以及接种疫苗。BTV疫苗接种的目的是预防临床疾病，防止新的动物被感染，并允许动物从感染地区安全移动。2008年，英国开始自愿接种BTV-8灭活疫苗。灭活（改良活）和灭活BTV疫苗都已使用，但它们都有许多缺点。主要的问题是，由一种血清型BTV诱导的免疫仅保护免受相同血清型的感染。改良活病毒疫苗生产成本低廉，单次接种后可产生保护性免疫力，可在某些易感品种的绵羊中诱发临床疾病，并有可能通过蠓传播，有可能变回可导致严重疾病的病毒。虽然如果生产得当，灭活疫苗是安全的，但很难确定动物是否已被感染或接种疫苗;生产成本很高，不同品种的动物对疫苗接种的反应存在明显差异。由于目前的灭活BTV-8疫苗完全是BTV血清型特异性的，因此需要开发一种新的疫苗来抵御BTV-1和BTV-6对英国的潜在威胁，从而增加了实验室诊断和疫苗分发的成本。诱导免疫反应，保护对一些不同的BTV血清型可以发挥重要作用，在开发一个更广泛的交叉保护BTV疫苗。尽管BTV的抗体倾向于对BTV类型特异性，但有证据表明细胞介导的免疫（T细胞）更具交叉反应性。然而，T细胞在抗BTV中的作用尚不清楚。在这个项目中，我们将研究细胞介导的免疫在牛BTV感染后恢复中的作用。这些研究的结果将确定负责保护的免疫反应的要素，这些信息将促进新的BT疫苗策略的开发。

Bluetongue (BT) is an economically important infectious disease of sheep, cattle, goats and deer caused by bluetongue virus (BTV), which is spread by types of biting midges. Animals infected with BTV develop fever, reddening and swelling of the lips, mouth, nasal passages and eyelids, lose condition rapidly, develop muscle degeneration and lameness and may die from the disease. There are at least 24 different types of BTV and, until recently, the disease was largely confined to regions within Africa, Asia, the Americas and Australia. However, as a result of climate change and warmer weather in Europe, BTV-infected midges spread into southern Europe and in 2006 an outbreak of bluetongue occurred in some northern European countries. This was the first time that BTV has been known in northern Europe and in August 2007, the virus spread to the UK. During late 2007/early 2008 BTV serotype 1 arrived in southern France and its distribution overlaps with BTV-8. This raises the possibility that these strains of virus will exchange genes. This may enhance the ability of BTV-1 mixed progeny strains to spread northwards and increase the threat of a second serotype (BTV-1) in northern Europe and the UK. During 2008, a third strain of virus, BTV-6, was detected in the Netherlands and Germany. Control measures in recently infected countries include restrictions on animal movement, which have a significant economic impact, and vaccination. The aims of BTV vaccination are to prevent clinical disease; prevent new animals becoming infected and to allow the safe movement of animals from infected areas. Voluntary vaccination with an inactivated BTV-8 vaccine was introduced into the UK in 2008. Both disabled (modified live) and killed BTV vaccines have been used, but they both have a number of shortcomings. The main problem is that immunity induced by one serotype of BTV only protects against infection with the same serotype. Modified live virus vaccines, which are cheap to produce and generate protective immunity after a single dose, can induce clinical disease in certain susceptible breeds of sheep and have the potential to be spread by midges with the possibility of changing back to a virus that can cause severe disease. Although killed vaccines are safe if properly produced, it is difficult to determine whether animals have been infected or vaccinated; production costs are high and there are marked differences in the response of different breeds of animals to vaccination. Since the current inactivated BTV-8 vaccines are entirely BTV serotype specific, a new vaccine would need to be developed to protect against the potential threat to the UK of BTV-1 and BTV-6, increasing the cost of laboratory diagnosis and distribution of the vaccines. Induction of immune responses that protect against a number of different BTV serotypes could play a significant part in the development of a more widely cross-protective BTV vaccine. Whereas antibody to BTV tends to be serotype-specific, there is evidence that cell-mediated immunity (T cells) is more cross-reactive. However, the role of T cells in protection against BTV is not clear. In this project, we will investigate the role of cell-mediated immunity in recovery from BTV infection in cattle. The findings from these studies will identify elements of the immune response that are responsible for protection and this information will facilitate the development of novel BT vaccine strategies.