Effects of a nonapeptide thymic hormone on intestinal intraepithelial lymphocytes in mice following administration of 5-fluorouracil.
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.
Inagaki-Ohara
K
K
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University, School of Medicine, Japan.
Kobayashi
N
N
Nishimura
H
H
Sakai
T
T
Matsumoto
Y
Y
Hiromatsu
K
K
Awaya
A
A
Yoshikai
Y
Y
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004848:Epithelium / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005472:Fluorouracil / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013934:Thymectomy; D013935:Thymic Factor, Circulating / Q000494:pharmacology* / Q000627:therapeutic use
D016207:Cytokines; D012333:RNA, Messenger; D013935:Thymic Factor, Circulating; D005472:Fluorouracil