title: Physiological roles of gammadelta T-cell receptor intraepithelial lymphocytes in cytoproliferation and differentiation of mouse intestinal epithelial cells.
abstract: In this study we aimed to elucidate the physiological role of gammadelta intraepithelial lymphocytes (IEL) in the mouse intestine. For this purpose, we used T-cell receptor (TCR) Vgamma4/Vdelta5 transgenic mice (KN 6 Tg: BALB/c background, H-2d), and compared the immunological and physiological characteristics of the intestinal tracts of KN 6 Tg and non-transgenic (non-Tg) littermates. In KN 6 Tg littermates, 95% of small intestinal (SI) and large intestinal (LI) IEL expressed gammadelta TCR, and their TCR was replaced by Tg gammadelta TCR. In these mice, class II major histocompatibility complex (MHC) expression was up-regulated in the SI epithelium, compared with the non-Tg littermates, under specific pathogen-free (SPF) conditions. Competitive reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the mRNAs of the I-Ealpha chain on the SI epithelial cells was higher in KN 6 Tg than in non-Tg littermates. However, in the LI, class II MHC molecules were not expressed in either KN 6 Tg or non-Tg littermates. The epithelial cell mitotic index in the SI, but not in the LI, was higher in KN 6 Tg than in non-Tg littermates under SPF conditions. However, differentiation markers for SI epithelial cells, such as alkaline phosphatase and disaccharidase (lactase, maltase and sucrase) activities, were similar in KN 6 Tg and non-Tg littermates. MHC class II molecule expression on the SI epithelium was absent in germ-free (GF) Tg mice, but was induced under SPF conditions, coinciding with the increase of interferon-gamma (IFN-gamma) mRNA in gammadelta TCR SI-IEL. These findings suggest that gammadelta TCR IEL regulate epithelial cell regeneration and class II MHC expression, but not cell differentiation in the SI. However, these functions were not observed in the gammadelta TCR IEL in the LI. In addition, the activation step in the gammadelta TCR SI-IEL is dependent on the presence of gut microflora.
authors.affiliation: Yakult Central Institute for Microbiological Research, Yaho 1986, Kunitachi-shi, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Nanno
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Miyashita
authors.forename: H
authors.initials: H
authors.lastname: Amasaki
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Umesaki
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D004186:Disaccharidases / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology*; D007421:Intestine, Small / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000502:physiology*
chemical_list: D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma; D000469:Alkaline Phosphatase; D004186:Disaccharidases