Biotechnology Research Laboratories, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia.
Vet Res. 2010 Jul-Aug;41(4):37. doi: 10.1051/vetres/2010009. Epub 2010 Feb 2.
Sheep were sensitized by repeated infection with Haemonchus contortus L3, followed by a 12 week rest period, and an abomasal cannula was surgically implanted in all sheep. Seven of the sensitized sheep were subsequently challenged with 50 000 H. contortus L3 while 4 control sheep were challenged with saline. Biopsy samples were taken using a fibreoptic endoscope on days 0, 1, 2, 3, 5, 7 and 28 after challenge and leukocyte subpopulations quantified by (immuno)histology. Differential blood cell counts were performed on the same days. At the end of the trial, sheep showed significantly reduced worm burdens compared to unsensitized control sheep, confirming their resistance status. Both blood and tissue eosinophils, as well as tissue gammadelta TCR+ cells were rapidly elevated by day 1 post L3 challenge (pc), peaking at day 3 pc. There was a slight increase in tissue CD4 T cells at day 2 pc, peaking at day 3 pc while no significant changes in CD8 T cells were observed. B cells (CD45R+) increased later into challenged tissues with a peak at 5 days pc. All tissue lymphocyte subpopulations as well as tissue and blood eosinophils were reduced by day 7 pc before increasing again at day 28 pc, suggesting separate responses to larval and adult antigens. In contrast, globule leukocytes and mucosal mast cells only showed one peak at day 5 pc and 28 pc, respectively. Unexpectedly, globule leukocytes correlated significantly with tissue eosinophils but not mucosal mast cells. The results are consistent with an early eosinophil-mediated killing of L3, possibly recruited by IL-5 produced by gammadelta T cells. In contrast to post-mortem studies, abomasal cannulation allowed sequential analysis of both early and late time points in the same animal, providing a more complete picture of cellular interactions at both peripheral and local sites, and their correlation with the different stages of parasite development.
绵羊通过反复感染捻转血矛线虫 L3 致敏,然后休息 12 周,所有绵羊都通过手术植入了一个皱胃套管。随后,其中 7 只致敏绵羊接受了 50,000 条捻转血矛线虫 L3 的攻击,而 4 只对照绵羊则接受了盐水的攻击。在挑战后第 0、1、2、3、5、7 和 28 天,使用纤维内镜采集活检样本,并通过(免疫)组织学定量白细胞亚群。在相同的日子进行了全血白细胞分类计数。试验结束时,与未致敏对照绵羊相比,绵羊的蠕虫负担明显降低,证实了它们的抗性状态。在 L3 挑战后第 1 天(pc),血液和组织嗜酸性粒细胞以及组织 gammadelta TCR+细胞迅速升高(pc),在第 3 天 pc 时达到峰值。在第 2 天 pc 时,组织 CD4 T 细胞略有增加,在第 3 天 pc 时达到峰值,而 CD8 T 细胞没有明显变化。B 细胞(CD45R+)在第 5 天 pc 时才进入挑战组织,在第 5 天 pc 时达到峰值。在第 7 天 pc 之前,所有组织淋巴细胞亚群以及组织和血液嗜酸性粒细胞均减少,然后在第 28 天 pc 时再次增加,提示对幼虫和成虫抗原的单独反应。相比之下,球形体白细胞和黏膜肥大细胞仅在第 5 天 pc 和第 28 天 pc 时各出现一个高峰。出乎意料的是,球形体白细胞与组织嗜酸性粒细胞显著相关,但与黏膜肥大细胞无关。结果与早期嗜酸性粒细胞介导的 L3 杀伤一致,可能是由 gammadelta T 细胞产生的 IL-5 募集的。与死后研究不同,皱胃套管允许在同一动物中同时分析早期和晚期时间点,提供了外周和局部部位细胞相互作用及其与寄生虫发育不同阶段的相关性的更完整的图片。