Little Matthew C, Bell Louise V, Cliffe Laura J, Else Kathryn J
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
J Immunol. 2005 Nov 15;175(10):6713-22. doi: 10.4049/jimmunol.175.10.6713.
Despite a growing understanding of the role of cytokines in immunity to the parasitic helminth Trichuris muris, the local effector mechanism culminating in the expulsion of worms from the large intestine is not known. We used flow cytometry and immunohistochemistry to characterize the phenotype of large intestinal intraepithelial lymphocytes (IEL) and lamina propria leukocytes (LPL) from resistant and susceptible strains of mouse infected with T. muris. Leukocytes accumulated in the epithelium and lamina propria after infection, revealing marked differences between the different strains of mouse. In resistant mice, which mount a Th2 response, the number of infiltrating CD4+, CD8+, B220+, and F4/80+ IEL and LPL was generally highest around the time of worm expulsion from the gut, at which point the inflammation was dominated by CD4+ IEL and F4/80+ LPL. In contrast, in susceptible mice, which mount a Th1 response, the number of IEL and LPL increased more gradually and was highest after a chronic infection had developed. At this point, CD8+ IEL and F4/80+ LPL were predominant. Therefore, this study reveals the local immune responses underlying the expulsion of worms or the persistence of a chronic infection in resistant and susceptible strains of mouse, respectively. In addition, for the first time, we illustrate isolated lymphoid follicles in the large intestine, consisting of B cells interspersed with CD4+ T cells and having a central zone of rapidly proliferating cells. Furthermore, we demonstrate the organogenesis of these structures in response to T. muris infection.
尽管人们对细胞因子在抵抗寄生性蠕虫毛首鞭形线虫免疫中的作用有了越来越多的了解,但导致蠕虫从大肠排出的局部效应机制仍不清楚。我们使用流式细胞术和免疫组织化学来表征感染毛首鞭形线虫的抗性和易感小鼠品系的大肠上皮内淋巴细胞(IEL)和固有层白细胞(LPL)的表型。感染后白细胞在上皮和固有层中积聚,揭示了不同小鼠品系之间的显著差异。在产生Th2反应的抗性小鼠中,浸润的CD4 +、CD8 +、B220 +和F4/80 + IEL和LPL的数量通常在蠕虫从肠道排出时最高,此时炎症以CD4 + IEL和F4/80 + LPL为主。相比之下,在产生Th1反应的易感小鼠中,IEL和LPL的数量增加更为缓慢,并且在慢性感染发展后最高。此时,CD8 + IEL和F4/80 + LPL占主导地位。因此,本研究分别揭示了抗性和易感小鼠品系中蠕虫排出或慢性感染持续存在的局部免疫反应。此外,我们首次展示了大肠中的孤立淋巴滤泡,其由散布着CD4 + T细胞的B细胞组成,并具有快速增殖细胞的中心区域。此外,我们证明了这些结构在响应毛首鞭形线虫感染时的器官发生。