Defining the minimal signals necessary to generate an encephalitogenic T cell (IRC8P.476)
| Autor: | Priscilla Lee, Yuhong Yang, Michael Racke, Amy Lovett-Racke |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:190.4-190.4 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | While it is generally accepted that Multiple Sclerosis (MS) is a T cell-mediated disease, the factors determining the encephalitogenicity of T cells remains unclear. Myelin-specific T cells generated with antigen presenting cells (APCs) plus myelin peptide are encephalitogenic, whereas T cells generated with anti-CD3/CD28 antibodies are not, suggessting that APCs provide critical signals beyond T cell receptor activation and co-stimulation, contributing to an encephalitogenic phenotype. To recapitulate the signals provided by APCs, naïve myelin-specific CD4+ T cells were activated with anti-CD3/CD28 in the presence of various cytokines. The degree of encephalitogenicity of T cells was examined by the severity of experimental autoimmune encephalomyelitis (EAE). Although no single cytokine was sufficient, the combination of IL-6/IL-23 or IL-12/IL-23 generated highly encephalitogenic T cells. IL-6 and IL-12 induced the initial expression of IL-23R on naïve T cells, and IL-23 further enhanced the expression of its own receptor and the encephalitogenicity. Neutralizing IL-6 or IL-12 with antibodies significantly reduced the severity of EAE, which was induced by APC-generated T cells. We have identified that IL-6/IL-23 or IL-12/IL-23 combination in addition to TCR activation and co-stimulation were the miminal signals necessary to generate encephalitogenic T cells. This provides potential targets that can be manipulated therapeutically, resulting in innovative treatments for MS. |
| Databáze: | OpenAIRE |
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