title: An islet-specific pulse of TGF-β abrogates CTL function and promotes β cell survival independent of Foxp3+ T cells.
abstract: Effective therapies that prevent chronic inflammation from developing into type 1 diabetes remain elusive. In this study, we show that expression of TGF-β for just 1 wk in inflamed islets of NOD mice significantly delays diabetes development. Time course studies demonstrated that the brief TGF-β pulse protects only if administered when extensive β cell destruction has occurred. Surprisingly, TGF-β-mediated protection is not linked to enhanced Foxp3(+) regulatory T cell activity or to decreased intrapancreatic presentation of islet Ags. Instead, TGF-β disables the transition of primed autoreactive CD8(+) T cells to cytotoxic effectors and decreases generation, or maintenance, of CD8(+) memory T cells within the pancreas, significantly impairing their diabetogenic capacity.
authors.affiliation: Department of Pathology, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Maja
authors.initials: M
authors.lastname: Wållberg
authors.forename: F Susan
authors.initials: FS
authors.lastname: Wong
authors.forename: E Allison
authors.initials: EA
authors.lastname: Green
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000502:physiology; D007156:Immunologic Memory / Q000235:genetics; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000502:physiology; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000502:physiology
chemical_list: D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018836:Inflammation Mediators; D016212:Transforming Growth Factor beta