title: Induction of interferon-gamma, interleukin-4, and transforming growth factor-beta in rats orally tolerized against experimental autoimmune myasthenia gravis.
abstract: Oral administration of nicotinic acetylcholine receptor (AChR) to Lewis rats prior to myasthenogenic immunization with Torpedo AChR+complete Freund's adjuvant (CFA) results in the prevention of experimental autoimmune myasthenia gravis (EAMG) and the suppression of AChR-specific B cell responses and counteracts the development of AChR-reactive interferon-gamma (IFN-gamma) secreting T cells. To study the involvement of the T helper type 1 (Th1) cell-related lymphokine IFN-gamma, the Th2 cell-related interleukin-4 (IL-4), and transforming growth factor beta (TGF-beta) that suppresses the synthesis of IFN-gamma and IL-4, we used in situ hybridization with complementary DNA oligonucleotide probes to enumerate mononuclear cells (MNC) expressing mRNA for the cytokines IFN-gamma, IL-4, and TGF-beta. Upon in vivo recognition of AChR, popliteal, inguinal, and mesenteric lymph nodes, spleen and thymus of rats with EAMG contained higher levels of IFN-gamma, IL-4, and TGF-beta mRNA-expressing cells compared to CFA-injected control rats, implicating the involvement in EAMG of AChR-reactive Th1 and Th2 cells in parallel. TGF-beta was also upregulated in EAMG. Oral tolerance to EAMG was characterized by suppression of the levels of MNC expressing IFN-gamma and IL-4, but augmentation of cells expressing TGF-beta. The results suggest that IFN-gamma, IL-4, and TGF-beta are involved in the development of EAMG, and that TGF-beta is important in the induction of oral tolerance to EAMG.
authors.affiliation: Department of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Link
authors.forename: A
authors.initials: A
authors.lastname: Ljungdahl
authors.forename: B
authors.initials: B
authors.lastname: Höjeberg
authors.forename: J
authors.initials: J
authors.lastname: Link
authors.forename: B
authors.initials: B
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Qiao
authors.forename: A
authors.initials: A
authors.lastname: Melms
authors.forename: T
authors.initials: T
authors.lastname: Olsson
mesh_terms: D000818:Animals; D015870:Gene Expression; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008221:Lymphoid Tissue / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011978:Receptors, Nicotinic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D004676:Myelin Basic Protein; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma