Effects of a Nonapeptide Thymic Hormone on Intestinal Intraepithelial Lymphocytes in Mice Following Administration of 5-Fluorouracil

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 differentiationin 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 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 β1in 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 ofEnterobactericeae.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.