Reversal of autoimmune encephalomyelitis by membranes presenting myelin basic protein-associated class II MHC molecule as an approach to immunotherapy of organ-specific autoimmune diseases.
Experimental autoimmune encephalomyelitis (EAE), a well-accepted experimental model for multiple sclerosis in humans, is a paralytic disease mediated by CD4+ T cells specific for myelin basic protein (MBP). Several approaches to immune-specific therapy of EAE as a model for other organ-specific autoimmune diseases have previously been reported. We now show that macrophages (M phi) or B cells, as antigen-presenting cells, when pulsed with MBP and intraperitoneally (but not intravenously) inoculated after the encephalitogenic challenge, are highly effective in blocking the development of EAE. Moreover, M phi pulsed with an organ tissue homogenate, mouse spinal cord homogenate, can also present the relevant target antigen, MBP, and are as effective as MBP-pulsed M phi in blocking the development of EAE. This capacity of the M phi to identify and present the relevant target antigen indicates that this approach is also applicable to organ-specific autoimmune diseases other than EAE, regardless of how much is known about their etiological agent or specific target antigen. Nonviable glutaraldehyde-fixed MBP-pulsed M phi or membranes derived from MBP-pulsed M phi retain their capacity to block the development of EAE.
Ben-Nun
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Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Yossefi
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D005976:Glutaral / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007167:Immunotherapy; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D005976:Glutaral