title: Development of TCR alpha beta CD8 alpha alpha intestinal intraepithelial lymphocytes is promoted by interleukin-15-producing epithelial cells constitutively stimulated by gram-negative bacteria via TLR4.
abstract: The microbes present in the intestine have a strong influence on the development and maturation of lymphoid organs. The cross-talk mechanisms between intestinal intraepithelial lymphocytes (i-IEL) and noninvasive microbes are still poorly understood. The influence of microbes and lipopolysaccharides on the development of i-IEL, especially the TCR alpha beta(+) CD8 alpha alpha subset, was investigated using the different TLR4-mutant mouse strains C3H/HeJ, BALB/lps(d), and C57BL/10ScCr. Intestinal epithelial cells (i-EC) from TLR4-mutant strains did not express interleukin (IL)-15 mRNA, while IL-15 mRNA expression in i-EC from the corresponding wild-type, C3H/He, BALB/c, and C57BL/10ScSn mice was detected. The development of TCR alpha beta(+) CD8 alpha alpha cells in i-IEL significantly decreased in TLR4-mutant mice compared with the corresponding wild-type mice, while other T cell subsets in i-IEL showed similar percentages in the TLR4-mutant and wild-type mice. Adult thymectomized (ATx-) and lethally irradiated C3H/HeJ mice reconstituted with T cell-depleted bone marrow cells from C3H/He mice showed a significantly lower percentage of TCR alpha beta CD8 alpha alpha i-IEL than ATx-C3H/He mice after transfer of C3H/HeJ BM cells. The percentage of TCR alpha beta CD8 alpha alpha i-IEL and IL-15 mRNA expression in i-EC from BALB/lps(d) mice did not increase during Salmonella typhimurium infection but was significantly enhanced during Listeria monocytogenes infection. Our findings suggest that LPS induces IL-15 production by i-EC, resulting in the development of TCR alpha beta CD8 alpha alpha i-IEL.
authors.affiliation: Department of Biosciences, School of Science, Kitasato University, Sagamihara, Kanagawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kaneko
authors.forename: Tsunehide
authors.initials: T
authors.lastname: Mizunuma
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takimoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kumazawa
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012486:Salmonella typhimurium / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D019409:Interleukin-15; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors