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International Immunology
Year: 2010  |  Volume: 22  |  Issue: 10  |  Page No.: 817 - 826

Targeting ganglioside epitope 3G11 on the surface of CD4+ T cells suppresses EAE by altering the Treg/Th17 cell balance

Z Zhao, B Ciric, S Yu, G. X Zhang and A. Rostami    

Abstract:

Loss of expression of the 3G11 epitope, present on disialoceramide that is predominantly found on CD4+ T cells, has been associated with a regulatory T cell (Treg) phenotype and tolerance induction in experimental autoimmune encephalomyelitis (EAE). Here we report that treatment with anti-3G11 mAb shifts the immune response from pro-inflammatory to tolerogenic and suppresses both chronic-progressive and relapsing–remitting EAE. This therapeutic effect can be achieved at different stages of EAE. Treatment with anti-3G11 mAb increased the proportion of Foxp3+CD25+CD4+ Tregs and IL-10 production while inhibiting production of pro-inflammatory cytokines and responsiveness to IL-2 and decreasing the proportion of Th17 cells. The effect of anti-3G11 mAb was diminished in IL-10–/– mice, indicating that this cytokine mediates some of its effects. As 3G11 belongs to the ganglioside family, which is expressed on the surface of both murine and human CD4+ T cells, targeting this class of molecules may provide a novel approach for treating autoimmune diseases.

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