Sasaki K, Bean A, Shah S, Schutten E, Huseby PG, Peters B, Shen ZT, Vanguri V, Liggitt D, Huseby ES.Relapsing-Remitting Central Nervous System Autoimmunity Mediated by GFAP-Specific CD8 T Cells.J Immunol. 2014 Mar. [Epub ahead of print]
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.
The conclusions say it all for too long MS specialitist have made their view of MS based on a few EAE models and have focussed on CD4 T cells and myelin basic protein. this study shows that if you get immune responses to other proteins you can get the same disease. This warns us that thinking that MS is an autoimmune disease to a single target is probably not going to be the case.