Treatment of spinal cord-induced experimental allergic encephalomyelitis in the Lewis rat with liposomes presenting central nervous system antigens.
Chronic-relapsing experimental allergic encephalomyelitis (CR-EAE) in the Lewis rat, induced by the injection of spinal cord tissue in complete Freund's adjuvant (SC/CFA), was studied in vivo by treatment with liposomes containing central nervous tissue antigens, and in vitro by lymphocyte proliferation assays. Intracardiac administration of myelin basic protein (MBP) liposomes, galactocerebroside (GC) liposomes, or MBP + GC liposomes substantially reduced the clinical severity and/or delayed the onset of the initial phase of disease. Liposomes prepared from whole myelin provided even greater protection, and were effective at suppressing both the first disease episode and the relapses. These results indicate that while GC and MBP may play significant roles in the development of CR-EAE in the Lewis rat, immune responses to other antigens are probably also involved. Splenic and lymph node lymphocytes from MBP-GC liposome-treated rats, and splenic lymphocytes from cytochrome-GC (CYT-GC) liposome-treated rats, showed drastically reduced abilities to proliferate in response to MBP in culture. Spleen cells from both the MBP-GC- and CYT-GC-liposome-treated donors were able to actively suppress antigen-induced proliferation of MBP-primed lymphocytes. These findings suggest participation of both clonal anergy, and active suppressor cells in the liposome-mediated suppression of CR-EAE in the Lewis rat.
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
C S
CS
Stein
J
J
St Louis
J J
JJ
Gilbert
G H
GH
Strejan
D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000627:therapeutic use; D002455:Cell Division; D002490:Central Nervous System / Q000276:immunology*; D003574:Cytochrome c Group / Q000008:administration & dosage / Q000627:therapeutic use; D004337:Drug Carriers; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D005699:Galactosylceramides / Q000008:administration & dosage / Q000627:therapeutic use; D006168:Guinea Pigs; D008081:Liposomes; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000627:therapeutic use; D009417:Nerve Tissue / Q000637:transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D013116:Spinal Cord
D000941:Antigens; D003574:Cytochrome c Group; D004337:Drug Carriers; D005699:Galactosylceramides; D008081:Liposomes; D004676:Myelin Basic Protein; C002454:galactocerebroside