Sandor M, Sperling A I, Cook G A, Weinstock J V, Lynch R G, Bluestone J A
Department of Pathology, College of Medicine, University of Iowa, Iowa City 52242, USA.
J Immunol. 1995 Jul 1;155(1):275-84.
Isolated granulomas provide a unique model to study T cells in the site of inflammation. Schistosoma mansoni-infected mice develop liver granulomas in response to schistosome egg deposition and the granulomas contain gamma delta T cells that appear to be activated (Pgp-1high and L-selectin low). Analysis of kinetics and TCR gene usage of granuloma gamma delta T cells revealed a limited TCR repertoire restricted to V gamma 1.1, V delta 4, and V delta 6 genes, suggesting that the occurrence of gamma delta T cells in the granuloma is influenced by TCR V gene usage. The V delta 4+, but not the V delta 6+, gamma delta T cells expressed CD69, a marker of recent activation. To determine if there was a preferred order of accumulation of the gamma delta T cells in granulomas, s.c. sponge grafts were implanted into schistosome-infected mice, schistosome eggs were injected into the grafts, and accumulated T cells were sequentially analyzed. The earliest gamma delta T cell immigrants expressed V delta 6 and later immigrants expressed V delta 4 V genes. Additional evidence for a role of TCR specificity in the accumulation of gamma delta T cells in granulomas is their absence from schistosome granulomas in TCR transgenic mice that express only a single MHC-specific gamma delta TCR. Finally, gamma delta T cell recruitment into the granulomas did not require beta 2-microglobulin, since gamma delta T cells were present in liver granulomas of beta 2-microglobulin gene-disrupted mice. The analysis of the influx of gamma delta T cells into schistosome-induced, liver granulomas and schistosome egg-containing sponges provides a model system to investigate the role, if any, of gamma delta T cells in schistosome infections.
孤立性肉芽肿为研究炎症部位的T细胞提供了一个独特的模型。感染曼氏血吸虫的小鼠会因血吸虫卵沉积而形成肝脏肉芽肿，这些肉芽肿含有似乎被激活的γδ T细胞（Pgp-1高表达且L-选择素低表达）。对肉芽肿γδ T细胞的动力学和TCR基因使用情况的分析表明，其TCR库有限，仅限于Vγ1.1、Vδ4和Vδ6基因，这表明肉芽肿中γδ T细胞的出现受TCR V基因使用情况的影响。Vδ4 +的γδ T细胞而非Vδ6 +的γδ T细胞表达CD69，这是近期激活的标志物。为了确定γδ T细胞在肉芽肿中的积累是否存在优先顺序，将皮下海绵移植物植入感染血吸虫的小鼠体内，向移植物中注射血吸虫卵，并对积累的T细胞进行序列分析。最早迁移的γδ T细胞表达Vδ6，随后迁移的细胞表达Vδ4 V基因。TCR特异性在肉芽肿中γδ T细胞积累中起作用的另一证据是，在仅表达单一MHC特异性γδ TCR的TCR转基因小鼠的血吸虫肉芽肿中不存在γδ T细胞。最后，γδ T细胞募集到肉芽肿中不需要β2-微球蛋白，因为在β2-微球蛋白基因敲除小鼠的肝脏肉芽肿中存在γδ T细胞。对γδ T细胞流入血吸虫诱导的肝脏肉芽肿和含血吸虫卵海绵的分析提供了一个模型系统，以研究γδ T细胞在血吸虫感染中的作用（如果有）。
