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Suppression of experimental allergic encephalomyelitis by MBP-coupled lymphoid cells and by MBP-liposomes: a
1Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Abstract:
In previous experiments, we showed that administration of myelin basic protein (MBP) inserted into phosphatidyl-serine liposomes, to susceptible animals suppressed the clinical manifestations of both acute and chronic-relapsing EAE. In this report we compare the effectiveness of treatment with MBP-liposomes and with MBP-coupled syngeneic spleen cells in EAE protection. Lewis rats treated with 150 micrograms MBP-liposomes or with 160 micrograms (35 x 10(6] MBP-coupled spleen cells, given 7 days before and 7 days after encephalitogenic challenge were equally protected against clinical EAE, when compared to untreated controls. In addition to clinical protection, in vitro proliferative responses of lymphocytes from treated rats were significantly reduced, but delayed hypersensitivity (DTH) reactions remained unaffected. Proliferation of lymphocytes from MBP-sensitized donors was inhibited by the addition of spleen cells but not of lymph node cells from treated donors. The inhibitory effect was observed with spleen cells regardless of whether the donors were treated or not, was antigen nonspecific, and localized in a radio-resistant, adherent cell population. Adoptive transfers of spleen cells from treated donors, after a 48-hr in vitro incubation with concanavalin A, showed that the cells from donors treated with MBP-coupled spleen cells, but not with MBP-liposomes, suppressed the disease in recipients, following challenge with MBP-complete Freund's adjuvant (CFA). These results suggest that two distinct mechanisms operate in the protection by MBP-coupled cells and MBP-liposomes, respectively.
Insights
Both myelin basic protein (MBP)-liposomes and MBP-coupled spleen cells equally protect against experimental autoimmune encephalomyelitis (EAE). However, distinct mechanisms underlie their protective effects, with spleen cells showing antigen-nonspecific inhibition.
Area of Science:
- Immunology
- Neuroscience
Background:
- Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis.
- Myelin basic protein (MBP) is a key autoantigen in EAE.
- Previous studies demonstrated MBP-liposomes suppress EAE.
Purpose of the Study:
- To compare the efficacy of MBP-liposomes and MBP-coupled syngeneic spleen cells in EAE protection.
- To elucidate the underlying mechanisms of protection offered by each treatment.
Main Methods:
- Lewis rats were treated with MBP-liposomes or MBP-coupled spleen cells before and after encephalitogenic challenge.
- Clinical EAE manifestations were assessed.
- In vitro lymphocyte proliferation and delayed hypersensitivity (DTH) reactions were measured.
- Adoptive transfer experiments using spleen cells from treated donors were performed.
Main Results:
- Both MBP-liposomes and MBP-coupled spleen cells provided equal clinical protection against EAE.
- In vitro lymphocyte proliferation was reduced in treated rats, while DTH reactions were unaffected.
- Spleen cells from treated donors, but not lymph node cells, inhibited lymphocyte proliferation.
- Adoptive transfer of in vitro-activated spleen cells from MBP-coupled cell-treated donors suppressed EAE in recipients.
Conclusions:
- MBP-liposomes and MBP-coupled spleen cells offer comparable protection against EAE.
- Distinct mechanisms mediate the protective effects of MBP-liposomes and MBP-coupled spleen cells.
- MBP-coupled spleen cells induce antigen-nonspecific, radio-resistant suppressor cell activity.