Induction of interferon-gamma, interleukin-4, and transforming growth factor-beta in rats orally tolerized against experimental autoimmune myasthenia gravis.
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.
Wang
Z Y
ZY
Department of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Link
H
H
Ljungdahl
A
A
Höjeberg
B
B
Link
J
J
He
B
B
Qiao
J
J
Melms
A
A
Olsson
T
T
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*
D004676:Myelin Basic Protein; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma