Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factorin situ

Proceedings of the National Academy of Sciences of the United States of America - Tập 100 Số 24 - Trang 14157-14162 - 2003
Rina Aharoni1, Başak Kayhan1, Raya Eilam1, Michael Sela1, Ruth Arnon1
1Departments of Immunology and Veterans Resources, The Weizmann Institute, Rehovot 76100, Israel

Tóm tắt

The ability of a remedy to modulate the pathological process in the target organ is crucial for its therapeutic activity. Glatiramer acetate (GA, Copaxone, Copolymer 1), a drug approved for the treatment of multiple sclerosis, induces regulatory T helper 2/3 cells that penetrate the CNS. Here we investigated whether these GA-specific T cells can function as suppressor cells with therapeutic potential in the target organ byin situexpression of T helper 2/3 cytokines and neurotrophic factors. GA-specific cells and theirin situexpression were detected on the level of whole-brain tissue by using a two-stage double-labeling system: (i) labeling of the GA-specific T cells, followed by their adoptive transfer, and (ii) detection of the secreted factors in the brain by immunohistological methods. GA-specific T cells in the CNS demonstrated intense expression of the brain-derived neurotrophic factor and of two antiinflammatory cytokines, IL-10 and transforming growth factor β. No expression of the inflammatory cytokine IFN-γ was observed. This pattern of expression was manifested in brains of normal and experimental autoimmune encephalomyelitis-induced mice to which GA-specific cells were adoptively transferred, but not in control mice. Furthermore, infiltration of GA-induced cells to the brain resulted in bystander expression of IL-10 and transforming growth factor β by resident astrocytes and microglia. The ability of infiltrating GA-specific cells to express antiinflammatory cytokines and neurotrophic factor in the organ in which the pathological processes occur correlates directly with the therapeutic activity of GA in experimental autoimmune encephalomyelitis/multiple sclerosis.

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Tài liệu tham khảo

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Proceedings of the National Academy of Sciences of the United States of America

Tập 100 Số 24

14157-14162

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