BACKGROUND: Alpha-galactosylceramide (alpha-GalCer) is an invariant natural killer T (iNKT) cell ligand that prevents type 1 diabetes in NOD mice. However, alpha-GalCer can activate or suppress immune responses, raising concern about its potential use in human diabetes. MATERIALS AND METHODS: To evaluate this therapeutic issue further, BBDR and LEW.1WR1 rats were treated with Kilham rat virus (KRV) plus polyinosinic-polycytidylic acid, with or without alpha-GalCer, and followed for onset of diabetes. RESULTS: alpha-GalCer did not prevent diabetes in inducible rat models. To investigate this discrepancy, we analyzed iNKT cell function. Splenocytes stimulated with alpha-GalCer produced similar levels of IFNgamma in all rat strains, but less than mouse splenocytes. Rat splenocytes stimulated with alpha-GalCer preferentially produced IL-12, whereas mouse splenocytes preferentially produced IL-4. CONCLUSION: alpha-GalCer elicits species-specific cytokine responses in iNKT cells. In humans with type 1 diabetes, differences in iNKT cell responses to stimulation with alpha-GalCer due to age, genetic variability and other factors may influence its therapeutic potential.
BACKGROUND:Alpha-galactosylceramide (alpha-GalCer) is an invariant natural killer T (iNKT) cell ligand that prevents type 1 diabetes in NODmice. However, alpha-GalCer can activate or suppress immune responses, raising concern about its potential use in humandiabetes. MATERIALS AND METHODS: To evaluate this therapeutic issue further, BBDR and LEW.1WR1 rats were treated with Kilham rat virus (KRV) plus polyinosinic-polycytidylic acid, with or without alpha-GalCer, and followed for onset of diabetes. RESULTS:alpha-GalCer did not prevent diabetes in inducible rat models. To investigate this discrepancy, we analyzed iNKT cell function. Splenocytes stimulated with alpha-GalCer produced similar levels of IFNgamma in all rat strains, but less than mouse splenocytes. Rat splenocytes stimulated with alpha-GalCer preferentially produced IL-12, whereas mouse splenocytes preferentially produced IL-4. CONCLUSION:alpha-GalCer elicits species-specific cytokine responses in iNKT cells. In humans with type 1 diabetes, differences in iNKT cell responses to stimulation with alpha-GalCer due to age, genetic variability and other factors may influence its therapeutic potential.
Authors: T Kawano; J Cui; Y Koezuka; I Toura; Y Kaneko; K Motoki; H Ueno; R Nakagawa; H Sato; E Kondo; H Koseki; M Taniguchi Journal: Science Date: 1997-11-28 Impact factor: 47.728
Authors: S Sharif; G A Arreaza; P Zucker; Q S Mi; J Sondhi; O V Naidenko; M Kronenberg; Y Koezuka; T L Delovitch; J M Gombert; M Leite-De-Moraes; C Gouarin; R Zhu; A Hameg; T Nakayama; M Taniguchi; F Lepault; A Lehuen; J F Bach; A Herbelin Journal: Nat Med Date: 2001-09 Impact factor: 53.440
Authors: Y N Naumov; K S Bahjat; R Gausling; R Abraham; M A Exley; Y Koezuka; S B Balk; J L Strominger; M Clare-Salzer; S B Wilson Journal: Proc Natl Acad Sci U S A Date: 2001-11-13 Impact factor: 11.205
Authors: Peter T Lee; Amy Putnam; Kamel Benlagha; Luc Teyton; Peter A Gottlieb; Albert Bendelac Journal: J Clin Invest Date: 2002-09 Impact factor: 14.808
Authors: Danny Zipris; Jan-Luuk Hillebrands; Raymond M Welsh; Jan Rozing; Jenny X Xie; John P Mordes; Dale L Greiner; Aldo A Rossini Journal: J Immunol Date: 2003-04-01 Impact factor: 5.422
Authors: Elisa Monzon-Casanova; Daniel Paletta; Lisa Starick; Ingrid Müller; Derek B Sant'Angelo; Elwira Pyz; Thomas Herrmann Journal: Eur J Immunol Date: 2012-12-26 Impact factor: 5.532
Authors: Frederick R Roberts; Clinton Hupple; Elaine Norowski; Nicole C Walsh; Natalia Przewozniak; Ken-Edwin Aryee; Filia M Van Dessel; Agata Jurczyk; David M Harlan; Dale L Greiner; Rita Bortell; Chaoxing Yang Journal: PLoS One Date: 2017-06-12 Impact factor: 3.240
Authors: Natasha Qaisar; Adediwura Arowosegbe; Alan G Derr; Alper Kucukural; Basanthi Satish; Riccardo Racicot; Zhiru Guo; Melanie I Trombly; Jennifer P Wang Journal: Immunohorizons Date: 2021-10-26