Relapsing–Remitting Central Nervous System Autoimmunity Mediated by GFAP-Specific CD8 T Cells
| Autor: | Denny Liggitt, Vijay K. Vanguri, Eric S. Huseby, Elizabeth Schutten, Priya G. Huseby, Zu T. Shen, Katsuhiro Sasaki, Angela M. Bean, Shivanee Shah, Björn Peters |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:3029-3042 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1302911 |
| Popis: | Multiple sclerosis (MS) is an inflammatory disease of the CNS that causes the demyelination of nerve cells and destroys oligodendrocytes, neurons, and axons. Historically, MS has been thought to be a CD4 T cell–mediated autoimmune disease of CNS white matter. However, recent studies identified CD8 T cell infiltrates and gray matter lesions in MS patients. These findings suggest that CD8 T cells and CNS Ags other than myelin proteins may be involved during the MS disease process. In this article, we show that CD8 T cells reactive to glial fibrillary acidic protein (GFAP), a protein expressed in astrocytes, can avoid tolerance mechanisms and, depending upon the T cell–triggering event, drive unique aspects of inflammatory CNS autoimmunity. In GFAP-specific CD8 TCR-transgenic (BG1) mice, tissue resident memory-like CD8 T cells spontaneously infiltrate the gray matter and white matter of the CNS, resulting in a relapsing–remitting CNS autoimmunity. The frequency, severity, and remissions from spontaneous disease are controlled by the presence of polyclonal B cells. In contrast, a viral trigger induces GFAP-specific CD8 T effector cells to exclusively target the meninges and vascular/perivascular space of the gray and white matter of the brain, causing a rapid, acute CNS disease. These findings demonstrate that the type of CD8 T cell–triggering event can determine the presentation of distinct CNS autoimmune disease pathologies. |
| Databáze: | OpenAIRE |
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