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More MS news articles for November 2003

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

Proc Natl Acad Sci U S A. 2003 Nov 12
Aharoni R, Kayhan B, Eilam R, Sela M, Arnon R.
Departments of (*)Immunology and ()Veterans Resources, The Weizmann Institute, Rehovot 76100, Israel.

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 by in situ expression of T helper 2/3 cytokines and neurotrophic factors.

GA-specific cells and their in situ expression 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 beta.

No expression of the inflammatory cytokine IFN-gamma 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 beta 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.