Inagaki-Ohara K, Kobayashi N, Nishimura H, Sakai T, Matsumoto Y, Hiromatsu K, Awaya A, Yoshikai Y
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University, School of Medicine, Japan.
Cell Immunol. 1996 Jul 10;171(1):30-40. doi: 10.1006/cimm.1996.0169.
A significant fraction of murine small intestinal intraepithelial lymphocytes (i-IELs) mature in local sites outside the thymus. However, there is evidence suggesting that extrathymic differentiation of i-IELs is still influenced by the thymus or thymus-derived factors. Facteur thymique serique (FTS), a nonapeptide thymic hormone, is involved in several aspects of intra- and extrathymic T cell differentiation in vivo. In this study, we investigated the effects of FTS on the kinetics of i-IELs in mice following a single administration of 5-fluorouracil (5-FU). FTS treatment significantly accelerated the recovery in cell number of i-IELs after administration of 5-FU. Flow cytometric analysis revealed that this accelerated recovery was mainly due to a rapid increase in CD8 alpha alpha+ i-IELs. Similar findings were also evident in adult thymectomized (ATX) mice, indicating that FTS treatment caused a rapid recovery of CD8 alpha alpha+ i-IELs following 5-FU administration in the absence of a functional thymus. Furthermore, expression levels of the mRNAs for interleukin-2, interferon-gamma, and transforming growth factor beta 1 in the i-IELs were augmented by FTS treatment. Notably, FTS treatment protected mice from 5-FU-induced lethal toxicity, accompanied with an inhibition of the translocation of Enterobacteriaceae. These results suggest that FTS has an important function in the extrathymic maturation and activation of i-IELs in the small intestine following 5-FU administration, which may contribute at least partly to the protection against 5-FU-induced lethal toxicity.
相当一部分小鼠小肠上皮内淋巴细胞（i-IELs）在胸腺外的局部部位成熟。然而，有证据表明i-IELs的胸腺外分化仍受胸腺或胸腺衍生因子的影响。血清胸腺因子（FTS）是一种九肽胸腺激素，参与体内胸腺内和胸腺外T细胞分化的多个方面。在本研究中，我们探讨了FTS对单次给予5-氟尿嘧啶（5-FU）后小鼠i-IELs动力学的影响。FTS处理显著加速了5-FU给药后i-IELs细胞数量的恢复。流式细胞术分析显示，这种加速恢复主要是由于CD8αα+i-IELs的快速增加。在成年胸腺切除（ATX）小鼠中也有类似的发现，表明在没有功能性胸腺的情况下，FTS处理导致5-FU给药后CD8αα+i-IELs快速恢复。此外，FTS处理可提高i-IELs中白细胞介素-2、干扰素-γ和转化生长因子β1的mRNA表达水平。值得注意的是，FTS处理可保护小鼠免受5-FU诱导的致死毒性，同时抑制肠杆菌科细菌的易位。这些结果表明，FTS在5-FU给药后小肠i-IELs的胸腺外成熟和激活中具有重要作用，这可能至少部分有助于预防5-FU诱导的致死毒性。
