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.