Neutralizing antibodies to IFN-gamma-inducing factor prevent experimental autoimmune encephalomyelitis.
Specific oligonucleotide primers were used to identify and isolate IFN-gamma-inducing factor (IGIF) from the brain of rats with developing experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease of the central nervous system that serves as a model for multiple sclerosis. IGIF was highly transcribed in the brain at the onset and during the course of active EAE. PCR products encoding rat IGIF were used to generate the recombinant protein that was used to induce anti-IGIF neutralizing Abs. These Abs significantly reduced the production of IFN-gamma by primed T cells proliferating in response to their target myelin basic protein epitope and by Con A-activated T cells from naive donors. When administered to rats during the development of either active or transferred EAE, these Abs significantly blocked the development of disease. Splenic T cells from protected rats were cultured with the encephalitogenic myelin basic protein epitope and evaluated for production of IL-4 and IFN-gamma. These cells, which proliferated, exhibited a profound increase in IL-4 production that was accompanied by a significant decrease in IFN-gamma and TNF-alpha production. Thus, we suggest that perturbation of the Th1/Th2 balance toward Th2 cells is the mechanism underlying EAE blockade by anti-IGIF immunotherapy.
Wildbaum
G
G
Department of Immunology, Bruce Rappaport Faculty of Medicine, Haifa, Israel.
Youssef
S
S
Grabie
N
N
Karin
N
N
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D007106:Immune Sera; D020382:Interleukin-18; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma