title: Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis.
abstract: The synthetic amino acid copolymer copolymer 1 (Cop 1) suppresses experimental autoimmune encephalomyelitis (EAE) and is beneficial in multiple sclerosis. To further understand Cop 1 suppressive activity, we studied the cytokine secretion profile of various Cop 1-induced T cell lines and clones. Unlike T cell lines induced by myelin basic protein (MBP), which secreted either T cell helper type 1 (Th1) or both Th1 and Th2 cytokines, the T cell lines/clones induced by Cop 1 showed a progressively polarized development toward the Th2 pathway, until they completely lost the ability to secrete Th1 cytokines. Our findings indicate that the polarization of the Cop 1-induced lines did not result from the immunization vehicle or the in vitro growing conditions, but rather from the tendency of Cop 1 to preferentially induce a Th2 response. The response of all of the Cop 1 specific lines/clones, which were originated in the (SJL/JxBALB/c)F1 hybrids, was restricted to the BALB/c parental haplotype. Even though the Cop 1-induced T cells had not been exposed to the autoantigen MBP, they crossreacted with MBP by secretion of interleukin (IL)-4, IL-6, and IL-10. Administration of these T cells in vivo resulted in suppression of EAE induced by whole mouse spinal cord homogenate, in which several autoantigens may be involved. Secretion of anti-inflammatory cytokines by Cop 1-induced suppressor cells, in response to either Cop 1 or MBP, may explain the therapeutic effect of Cop 1 in EAE and in multiple sclerosis.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Aharoni
authors.forename: D
authors.initials: D
authors.lastname: Teitelbaum
authors.forename: M
authors.initials: M
authors.lastname: Sela
authors.forename: R
authors.initials: R
authors.lastname: Arnon
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D003429:Cross Reactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D000068717:Glatiramer Acetate; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D004676:Myelin Basic Protein / Q000276:immunology*; D010455:Peptides / Q000494:pharmacology*; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D004676:Myelin Basic Protein; D010455:Peptides; D015847:Interleukin-4; D000068717:Glatiramer Acetate