Date of Award
1985
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Abstract
Hartley guinea pig central nervous system (CNS) myelin was purified and fractionated. Both lyophilized and "wet" myelin induced chronic experimental allergic encephalomyelitis (EAE) in juvenile strain 13/N guinea pigs. Total myelin lipids (TL), galactocerebrosides (GC), gangliosides (GANG), phospholipids or proteolipids in association with a non-encephalitogenic dose (2ug) of MBP did not induce EAE; however, in MBP-TL animals, cell-mediated immune responses (CMI) were augmented. Only the proteolipids elicited delayed hypersensitivity. When TL was associated with an encephalitogenic dose (50ug) of MBP in CFA, juvenile strain 13 animals developed acute EAE with 100% recovery and 50% relapses.;Combinations of 50ug MBP and GC or GANG mixed with phosphatidyl choline (PC) and cholesterol (CHOL) in CFA, induced acute EAE in juvenile Hartleys with the highest recovery in MBP-GC animals. Controls that received MBP mixed with PC and CHOL (MBP-PC) or MBP alone, in CFA, developed acute EAE and died. Demyelination was present in the CNS during the acute attack except in the MBP-CFA group. Parameters of CMI correlated with clinicopathological findings only in MBP-GC and MBP-CFA animals. Serum anti-MBP and anti-lipid antibodies were detected at 10 and 90 days post-immunization (p.i.) respectively. Immune responses were not measurable in MBP-PC animals with EAE. All animals were refractory to rechallenge with MBP-CFA 90 days p.i. To investigate this suppression, donor strain 13 guinea pigs were immunized with MBP-GC or with MBP and TL without GC in CFA. Controls received dinitrophenylated-ovalbumin in CFA or CFA or IFA alone. Upon rechallenge with MBP-CFA 90 days p.i., only IFA pre-treated animals developed EAE. The in vitro proliferative response to MBP of syngeneic or allogeneic freshly MBP-CFA sensitized lymphocytes was suppressed by lymphocytes or their supernatants only from MBP-GC animals, isolated before or after rechallenge. Adoptive transfer of only MBP-GC spleen cells or their cell-free supernatants to naive syngeneic or allogeneic recipients respectively, prevented the induction of EAE.;The results indicate that myelin galactocerebrosides convert acute EAE to the chronic form possibly via antigen-specific suppressor cells which also may prevent active re-induction of disease. This suppression can be mediated by cell-free supernatants without MHC restriction.
Recommended Citation
Hosein, Zobeeda Zanimun, "Myelin Lipids In The Induction And Suppression Of Experimental Allergic Encephalomyelitis" (1985). Digitized Theses. 1451.
https://ir.lib.uwo.ca/digitizedtheses/1451