Cytokine Switch and Bystander Suppression of Autoimmune Responses to Multiple Antigens in Experimental Autoimmune Encephalomyelitis by a Single Recombinant T-Cell Receptor Ligand
| Autor: | Sushmita Sinha, Lisa Miller, Gregory G. Burrows, Thomas M. Proctor, Sandhya Subramanian, Arthur A. Vandenbark, Halina Offner, Chris Roberts |
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| Rok vydání: | 2009 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Recombinant Fusion Proteins T-Lymphocytes Encephalomyelitis medicine.medical_treatment Receptors Antigen T-Cell T-Cell Antigen Receptor Specificity Biology Ligands Article Mice Antigen medicine Bystander effect Animals Tissue Extracts General Neuroscience Multiple sclerosis T-cell receptor Experimental autoimmune encephalomyelitis Bystander Effect medicine.disease Cytokine Spinal Cord Immunology Cytokines Female Peptides |
| Zdroj: | The Journal of Neuroscience. 29:3816-3823 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.5812-08.2009 |
| Popis: | Recombinant T-cell receptor ligands (RTLs) can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner, and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). Antigen specificity of RTL raises the question as to whether this treatment would be successful in MS patients where target antigens are unknown. Using spinal cord homogenate or combinations of two different peptides to induce disease, we found that treatment with single RTL could reverse EAE as long as targeted T-cells were present. Therapy with three different RTLs each caused a significant reduction in IL-17 and increases in IL-10 and IL-13 in peptide-activated splenocytes, reduced proliferation of both cognate and bystander specificities of lymph node cells, and reduced inflammatory lesions and secreted IL-17 and IL-2 from peptide-activated spinal cord cells. These results show that treatment with single RTLs can induce a cytokine switch in cognate T-cells that inhibits both the target and bystander T-cells, providing new evidence for the potential applicability of RTL therapy in MS. |
| Databáze: | OpenAIRE |
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