Neutralizing antibodies to IFN-gamma-inducing factor prevent experimental autoimmune encephalomyelitis
| Autor: | G, Wildbaum, S, Youssef, N, Grabie, N, Karin |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Transcription Genetic Immune Sera Injections Subcutaneous Molecular Sequence Data Interleukin-18 Brain Epitopes T-Lymphocyte Th1 Cells Lymphocyte Activation Adoptive Transfer Recombinant Proteins Rats Interferon-gamma Th2 Cells Rats Inbred Lew T-Lymphocyte Subsets Animals Female Amino Acid Sequence Interleukin-4 RNA Messenger |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 161(11) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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