Antigen-specific immunosuppression: nasal tolerance to P0 protein peptides for the prevention and treatment of experimental autoimmune neuritis in Lewis rats.
Experimental autoimmune neuritis (EAN) is an autoimmune inflammatory demyelinating disease of the peripheral nervous system (PNS), and represents an animal model of the human Guillain-Barré syndrome (GBS). In this study, we report that nasal administration of the neuritogenic peptide 180-199 and of the cryptic peptide 56-71 of the rat neuritogenic P0 protein of peripheral nerve myelin prevents EAN and attenuates ongoing EAN. Both peptides effectively decreased the severity and shortened clinical EAN. Both a prophylactic and a therapeutic approach proved to be beneficial. These effects were associated with T and B cells hyporesponsiveness to the peptide antigens, reflected by downregulated Th1 cell responses (interferon-gamma secretion) and macrophage function, whereas Th2 cell responses (IL-4 secretion) and transforming growth factor-beta mRNA expression were upregulated.
Zou
L P
LP
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Ma
D H
DH
Levi
M
M
Wahren
B
B
Wei
L
L
Mix
E
E
van der Meide
P H
PH
Link
H
H
Zhu
J
J
D000281:Administration, Intranasal; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D004195:Disease Models, Animal; D000939:Epitopes; D015870:Gene Expression / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D018993:Myelin P0 Protein / Q000276:immunology* / Q000494:pharmacology*; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control*; D010446:Peptide Fragments / Q000494:pharmacology; D011129:Polyradiculoneuropathy / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000737:chemistry / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D018993:Myelin P0 Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma