Targeting ganglioside epitope 3G11 on the surface of CD4+ T cells suppresses EAE by altering the Treg/Th17 cell balance.
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 T(h)17 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.
Zhao
Zhao
Z
Department of Neurology, Suite 200, Jefferson Hospital for Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA.
Ciric
Bogoljub
B
Yu
Shuo
S
Zhang
Guang-Xian
GX
Rostami
Abdolmohamad
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005732:Gangliosides / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D005732:Gangliosides; C509654:antigen 3G11, mouse; D016753:Interleukin-10