Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Regulatory Th2-type T cell lines against insulin and GAD peptides derived from orally- and nasally-treated NOD mice suppress diabetes.
J Autoimmun. 1999 Jun;12(4):251-8. Unique Identifier : AIDSLINE MED/99264266 Maron R; Melican NS; Weiner HL; Brigham and Women's Hospital and Harvard Medical School, Center; for Neurologic Diseases, 77 Avenue Louis Pasteur, Boston, MA; 02115, USA.
Abstract:
Non-obese diabetic (NOD) mice spontaneously develop diabetes. Ourselves and others have previously shown that oral and nasal administration of insulin or glutamic acid decarboxylase (GAD) suppresses development of diabetes in the NOD mouse and that this suppression appears secondary to the generation of regulatory T cells that act by secreting anti-inflammatory cytokines such as IL-4 and TGF-beta. In the present study, we analysed cytokine patterns associated with mucosal administration of insulin B-chain, B-chain peptide 10-24 and GAD peptide 524-543 and derived lines and clones from mucosally-treated animals. Mice were fed five times (400-600 microg/feed) or nasally-treated three times (60 microg/application), and 2 days after the last treatment were immunized in the footpad with the mucosally administered antigen in CFA. Primary immune responses in the popliteal lymph node were measured 10 days after immunization and lines and clones were then established from the primary cultures. There was significantly less IFN-gamma production in mucosally-treated mice associated with increased production of IL-10 and TGF-beta. The nature of the antigen appeared to determine cytokine production as the B-chain given either orally or nasally primed for TGF-beta responses, whereas mucosally administered B-chain peptide 10-24 primed for IL-10. T cell clones, established from draining lymph nodes of fed or nasally-treated animals, secreted IL-4, IL-10 and TGF-beta whereas those from non-fed mice secreted IL-2 and IFN-gamma. Transfer of Th1 lines with splenocytes from diabetic NOD mice into NOD or NOD/SCID animals accelerated diabetes, whereas transfer of Th2 lines suppressed the development of diabetes. Our results further support a role for Th2-type cells in the regulation of diabetes in NOD mice. Copyright 1999 Academic Press.
Keywords: JOURNAL ARTICLE Administration, Intranasal Administration, Oral Adoptive Transfer Animal Cell Line Cytokines/BIOSYNTHESIS Diabetes Mellitus, Insulin-Dependent/*PREVENTION & CONTROL Female Glutamate Decarboxylase/*IMMUNOLOGY Immunization Insulin/*IMMUNOLOGY Mice Mice, Inbred NOD Peptide Fragments/IMMUNOLOGY Support, Non-U.S. Gov't Th1 Cells/PHYSIOLOGY Th2 Cells/*PHYSIOLOGY 990930
A9991376
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Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
