Polyreactive antibodies to glatiramer acetate promote myelin repair in murine model of demyelinating disease.
Using a murine model of demyelinating disease, we demonstrate that remyelination of spinal cord axons is promoted by antibodies to glatiramer acetate (GA, Copolymer-1, Copaxone), a therapeutic agent for multiple sclerosis (MS). Glatiramer acetate is a mixture of randomly synthesized peptides that induces both T cell activation and antibody production in all treated individuals. These observations prompted us to compare the independent effects of adoptively transferred GA-reactive T cells and antibodies in mice with chronic inflammatory demyelination induced by Theiler's virus. Transferred T cells had no effect on lesion load or the extent of remyelination. Purified polyclonal GA antibodies also did not alter lesion load, which suggests that neither GA T cells or antibodies were pathogenic. On the contrary, GA antibodies enhanced the normally low level of remyelination in chronic lesions. The antibodies, which were primarily immunoglobulin (Ig) G1 and IgG2, cross-reacted with oligodendrocytes, perivascular infiltrating cells, astrocytes, and neurons in spinal cord sections. In glial cultures they bound subsets of early lineage oligodendrocytes and microglia. Thus, several mechanisms may have contributed to the promotion of remyelination. These results support the hypothesis that the antibody response in GA-treated patients is beneficial by facilitating repair of demyelinated lesions.
Ure
Daren R
DR
Department of Immunology, Mayo Medical and Graduate School, Rochester, Minnesota 55905, USA.
Rodriguez
Moses
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D002908:Chronic Disease; D003429:Cross Reactions; D000068717:Glatiramer Acetate; D007114:Immunization; D051379:Mice; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D009186:Myelin Sheath / Q000473:pathology; D010455:Peptides / Q000276:immunology*; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D017945:Theilovirus; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000906:Antibodies; D010455:Peptides; D000068717:Glatiramer Acetate