Baldwin Cynthia L, Hsu Haoting, Chen Chuang, Palmer Mitchell, McGill Jodi, Waters W Ray, Telfer Janice C
University of Massachusetts Amherst, MA, USA.
University of Massachusetts Amherst, MA, USA.
Vet Immunol Immunopathol. 2014 Jun 15;159(3-4):144-55. doi: 10.1016/j.vetimm.2014.02.011. Epub 2014 Mar 3.
γδ T cells are critical to immune surveillance and protection since they are found as resident cells in many organs and tissues, including in humans and ruminants, and circulate at substantial numbers in the blood. It is known that γδ T cells contribute to cellular immunity and protection against important pathogens including organizing granulomas in response to Mycobacteria. We have shown that IFNγ-producing bovine γδ T cells bearing the WC1 co-receptor are the major cell population responding in recall responses to Leptospira during the first month following priming by vaccination against serovar Hardjo. To date, successful vaccines largely include those to diseases that only require antibody responses for protection and attempts at creating subunit peptide vaccines to stimulate conventional αβ T cells for cellular immune responses have been mostly unsuccessful. However, activation of nonconventional T cells, such as γδ T cells that direct adaptive T cell responses, has received little attention for improving vaccines because it is not clear how best to prime γδ T cells for recall responses. Annotation of the bovine genome showed there were 13 WC1 molecules coded for by individual genes. This gene number is conserved among breeds and individuals and expression of the WC1 molecules are distributed among cells to form a number of γδ T cell subsets. Using RNA silencing, we have shown that the WC1 co-receptor contributes to the ability of γδ T cells to respond to Leptospira spp. The Leptospira-responsive γδ T cells are found within a subset of the serologically defined WC1.1(+) γδ T cell subpopulation and our data indicate that the WC1 molecules expressed act as pattern recognition receptors interacting directly with bacterial components. We are now extending this work to Mycobacteria bovis.
γδ T细胞对免疫监视和保护至关重要,因为它们作为驻留细胞存在于包括人类和反刍动物在内的许多器官和组织中,并大量循环于血液中。已知γδ T细胞有助于细胞免疫,并抵御重要病原体,包括对分枝杆菌作出反应形成肉芽肿。我们已经表明,携带WC1共受体、产生IFNγ的牛γδ T细胞是在针对哈焦血清型进行疫苗接种引发后的第一个月内,对钩端螺旋体回忆反应中起主要作用的细胞群体。迄今为止,成功的疫苗主要包括那些针对仅需抗体反应即可提供保护的疾病的疫苗,而尝试创建亚单位肽疫苗以刺激传统αβ T细胞产生细胞免疫反应大多未成功。然而,非传统T细胞的激活,如指导适应性T细胞反应的γδ T细胞,在改进疫苗方面很少受到关注,因为尚不清楚如何最好地启动γδ T细胞以进行回忆反应。牛基因组注释显示,有13个WC1分子由单个基因编码。这个基因数量在不同品种和个体中是保守的,并且WC1分子的表达分布在细胞之间,形成多个γδ T细胞亚群。通过RNA沉默,我们已经表明WC1共受体有助于γδ T细胞对钩端螺旋体属作出反应的能力。对钩端螺旋体有反应的γδ T细胞存在于血清学定义的WC1.1(+)γδ T细胞亚群的一个子集中,我们的数据表明表达的WC1分子作为模式识别受体直接与细菌成分相互作用。我们现在正在将这项工作扩展到牛分枝杆菌。