BACKGROUND & AIMS: Invariant natural killer T (iNKT) cells undergo canonical, Vα14-Jα18 rearrangement of the T-cell receptor (TCR) in mice; this form of the TCR recognizes glycolipids presented by CD1d. iNKT cells mediate many different immune reactions. Their constitutive activated and memory phenotype and rapid initiation of effector functions after stimulation indicate previous antigen-specific stimulation. However, little is known about this process. We investigated whether symbiotic microbes can determine the activated phenotype and function of iNKT cells. METHODS: We analyzed the numbers, phenotypes, and functions of iNKT cells in germ-free mice, germ-free mice reconstituted with specified bacteria, and mice housed in specific pathogen-free environments. RESULTS: Specific pathogen-free mice, obtained from different vendors, have different intestinal microbiota. iNKT cells isolated from these mice differed in TCR Vβ7 frequency and cytokine response to antigen, which depended on the environment. iNKT cells isolated from germ-free mice had a less mature phenotype and were hyporesponsive to activation with the antigen α-galactosylceramide. Intragastric exposure of germ-free mice to Sphingomonas bacteria, which carry iNKT cell antigens, fully established phenotypic maturity of iNKT cells. In contrast, reconstitution with Escherichia coli, which lack specific antigens for iNKT cells, did not affect the phenotype of iNKT cells. The effects of intestinal microbes on iNKT cell responsiveness did not require Toll-like receptor signals, which can activate iNKT cells independently of TCR stimulation. CONCLUSIONS: Intestinal microbes can affect iNKT cell phenotypes and functions in mice.
BACKGROUND & AIMS: Invariant natural killer T (iNKT) cells undergo canonical, Vα14-Jα18 rearrangement of the T-cell receptor (TCR) in mice; this form of the TCR recognizes glycolipids presented by CD1d. iNKT cells mediate many different immune reactions. Their constitutive activated and memory phenotype and rapid initiation of effector functions after stimulation indicate previous antigen-specific stimulation. However, little is known about this process. We investigated whether symbiotic microbes can determine the activated phenotype and function of iNKT cells. METHODS: We analyzed the numbers, phenotypes, and functions of iNKT cells in germ-free mice, germ-free mice reconstituted with specified bacteria, and mice housed in specific pathogen-free environments. RESULTS: Specific pathogen-free mice, obtained from different vendors, have different intestinal microbiota. iNKT cells isolated from these mice differed in TCR Vβ7 frequency and cytokine response to antigen, which depended on the environment. iNKT cells isolated from germ-free mice had a less mature phenotype and were hyporesponsive to activation with the antigen α-galactosylceramide. Intragastric exposure of germ-free mice to Sphingomonas bacteria, which carry iNKT cell antigens, fully established phenotypic maturity of iNKT cells. In contrast, reconstitution with Escherichia coli, which lack specific antigens for iNKT cells, did not affect the phenotype of iNKT cells. The effects of intestinal microbes on iNKT cell responsiveness did not require Toll-like receptor signals, which can activate iNKT cells independently of TCR stimulation. CONCLUSIONS: Intestinal microbes can affect iNKT cell phenotypes and functions in mice.
Authors: Ya-Jen Chang; Hye Young Kim; Lee A Albacker; Hyun Hee Lee; Nicole Baumgarth; Shizuo Akira; Paul B Savage; Shin Endo; Takashi Yamamura; Janneke Maaskant; Naoki Kitano; Abel Singh; Apoorva Bhatt; Gurdyal S Besra; Peter van den Elzen; Ben Appelmelk; Richard W Franck; Guangwu Chen; Rosemarie H DeKruyff; Michio Shimamura; Petr Illarionov; Dale T Umetsu Journal: J Clin Invest Date: 2010-12-13 Impact factor: 14.808
Authors: Gerhard Wingender; Paul Rogers; Glenda Batzer; Myung Steve Lee; Dong Bai; Bo Pei; Archana Khurana; Mitchell Kronenberg; Anthony A Horner Journal: J Exp Med Date: 2011-05-30 Impact factor: 14.307
Authors: J L Matsuda; O V Naidenko; L Gapin; T Nakayama; M Taniguchi; C R Wang; Y Koezuka; M Kronenberg Journal: J Exp Med Date: 2000-09-04 Impact factor: 14.307
Authors: Jennifer L Matsuda; Laurent Gapin; Jody L Baron; Stéphane Sidobre; Daniel B Stetson; Markus Mohrs; Richard M Locksley; Mitchell Kronenberg Journal: Proc Natl Acad Sci U S A Date: 2003-06-26 Impact factor: 12.779
Authors: You Jeong Lee; Keli L Holzapfel; Jinfang Zhu; Stephen C Jameson; Kristin A Hogquist Journal: Nat Immunol Date: 2013-10-06 Impact factor: 25.606
Authors: Dingding An; Sungwhan F Oh; Torsten Olszak; Joana F Neves; Fikri Y Avci; Deniz Erturk-Hasdemir; Xi Lu; Sebastian Zeissig; Richard S Blumberg; Dennis L Kasper Journal: Cell Date: 2014-01-16 Impact factor: 41.582