Relapsing-remitting CNS autoimmunity mediated by GFAP-specific CD8 T cells
| Autor: | Sasaki, Katsuhiro, Bean, Angela, Shah, Shivanee, Schutten, Elizabeth, Huseby, Priya G., Peters, Bjorn, Shen, Zu T., Vanguri, Vijay, Liggitt, Denny, Huseby, Eric S. |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Central Nervous System
Mice Knockout Multiple Sclerosis Receptors Antigen T-Cell Brain Autoimmunity Mice Inbred Strains Mice Transgenic CD8-Positive T-Lymphocytes Flow Cytometry Immunohistochemistry Article Mice Inbred C57BL Interferon-gamma Mice Spinal Cord Central Nervous System Diseases Astrocytes Glial Fibrillary Acidic Protein Animals Cells Cultured |
| 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 have identified CD8 T cell infiltrates and gray matter lesions in MS patients. These findings suggest that CD8 T cells, and CNS antigens other than myelin proteins may be involved during the MS disease process. Here 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 T cell receptor 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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