Effects of a nonapeptide thymic hormone on intestinal intraepithelial lymphocytes in mice following administration of 5-fluorouracil

Kyoko Inagaki-Ohara, Noritada Kobayashi, Hitoshi Nishimura, Tetsu Sakai, Yoshihiro Matsumoto, Kenji Hiromatsu, Akira Awaya, Yasunobu Yoshikai

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    Abstract

    A significant fraction of murine small intestinal intraepithelial lymphocytes (i-IELs) maturate 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 viva. 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 CD8αα+ i- IELs. Similar findings were also evident in adult thymectomized (ATX) mice, indicating that FTS treatment caused a rapid recovery of CD8αα+ i-IELs following 5-FU administration in the absence of a functional thymus. Furthermore, expression levels of the mRNAs for interleukin-2, interferon- γ, and transforming growth factor β1 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 Enterobactericeae. 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.

    Original languageEnglish
    Pages (from-to)30-40
    Number of pages11
    JournalCellular Immunology
    Volume171
    Issue number1
    DOIs
    Publication statusPublished - Jul 10 1996

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    All Science Journal Classification (ASJC) codes

    • Immunology

    Cite this

    Inagaki-Ohara, K., Kobayashi, N., Nishimura, H., Sakai, T., Matsumoto, Y., Hiromatsu, K., ... Yoshikai, Y. (1996). Effects of a nonapeptide thymic hormone on intestinal intraepithelial lymphocytes in mice following administration of 5-fluorouracil. Cellular Immunology, 171(1), 30-40. https://doi.org/10.1006/cimm.1996.0169