EFFECTS OF A NONAPEPTIDE THYMIC HORMONE ON INTESTINAL INTRAEPITHELIALLYMPHOCYTES IN MICE FOLLOWING ADMINISTRATION OF 5-FLUOROURACIL

A significant fraction of murine small intestinal intraepithelial lymp hocytes (i-IELs) maturate in local sites outside the thymus. However, there is evidence suggesting that extrathymic differentiation of i-IEL s 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 vi vo. 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 n umber of i-IELs after administration of 5-FU. Flow cytometric analysis revealed that this accelerated recovery was mainly due to a rapid inc rease in CD8 alpha alpha(+) i-IELs. Similar findings were also evident in adult thymectomized (ATX) mice, indicating that FTS treatment caus ed a rapid recovery of CD8 alpha alpha(+) i-IELs following 5-FU admini stration in the absence of a functional thymus. Furthermore, expressio n levels of the mRNAs for interleukin-2, interferon-gamma, and transfo rming growth factor beta(1) in the i-IELs were augmented by FTS treatm ent. Notably, FTS treatment protected mice from 5-FU-induced lethal to xicity, accompanied with an inhibition of the translocation of Enterob actericeae. These results suggest that FTS has an important function i n the extrathymic maturation and activation of i-IELs in the small int estine following 5-FU administration, which may contribute at least pa rtly to the protection against 5-FU-induced lethal toxicity. (C) 1996 Academic Press, Inc.