Specific Th2 cells accumulate in the central nervous system of mice protected against experimental autoimmune encephalomyelitis by copolymer 1

This study addresses the issue of the effect of immunomodulating therapies in the target organ-the central nervous system (CNS)-in the case of multipl e sclerosis. Copolymer 1 (Cop 1. Copaxone, glatiramer acetate), an approved drug for the treatment of multiple sclerosis, is a potent inducer of Th2 r egulatory cells in both mice and humans. Highly reactive Cop 1-specific T c ell lines that secrete IL-4, IL-5. IL-6, IL-10. and transforming growth fac tor-p in response to Cop 1 and crossreact with myelin basic protein (MBP) a t the level of Th2 cytokine secretion were established from both brains and spinal cords of Cop 1-treated mice. In contrast, no reactivity to the cont rol antigen lysozyme could be obtained in lymphocytes isolated from CNS of mice injected with lysozyme. Adoptively transferred labeled Cop 1-specific suppressor cells were found in brain sections 7 and 10 days after their inj ection to the periphery, whereas lysozyme-specific cells were absent in the CNS. Hence, Cop 1-induced Th2 cells cross the blood-brain barrier and accu mulate in the CNS, where they can be stimulated in situ by MBP and thereby exert therapeutic effects in the diseased organ. This therapeutic effect wa s manifested, in brains of experimental autoimmune encephalomyelitis-induce d mice, by a decrease in the inflammatory cytokine interferon-gamma and by secretion of the antiinflammatory cytokine IL-10 in response to the autoant igen MBP.