Suppression of ongoing experimental autoimmune encephalomyelitis by neutralizing the function of the p28 subunit of IL-27.
IL-27 is a recently defined family member of the long-chain, four-helix bundle cytokines, which consist of EBI3, an IL-12p40-related protein, and p28, an IL-12p35-related polypeptide. The role of IL-27 in the regulation of experimental autoimmune encephalomyelitis has never been studied. We show in this study that neutralizing the in vivo function of IL-27 by Abs against IL-27 p28 rapidly suppressed an ongoing long-lasting disease in C57BL/6 mice. These Abs were then used to determine the mechanistic basis of disease suppression. We show in this study that IL-27 is involved not only in the polarization of naive T cells undergoing Ag-specific T cell activation, but also in promoting the proliferation and IFN-gamma production by polarized T cells, including the long term Th1 line that has been previously selected against the target encephalitogenic determinant. This may explain in part why neutralizing IL-27 suppresses an already established disease in a very rapid and significant manner.
Goldberg
Ruth
R
Department of Immunology, Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel.
Zohar
Yaniv
Y
Wildbaum
Gizi
G
Geron
Yifat
Y
Maor
Gila
G
Karin
Nathan
N
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007106:Immune Sera / Q000008:administration & dosage* / Q000096:biosynthesis; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D051381:Rats; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; C486767:Il27 protein, mouse; D007106:Immune Sera; D007378:Interleukins; C464565:MYDGF protein, human; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D007371:Interferon-gamma