4.3.1. Effector CD4+ T cells in MS
The onset of MS is caused by the activation of specific myelin-specific
T lymphocytes in the peripheral compartment, which gain access to the
CNS through the expression of appropriate adhesion molecules and
receptors in the BBB. Once inside the brain, T cells are reactivated by
self-antigens presented by resident APCs, leading to the manifestation
of the disease and demyelination of neurons. Research has shown that
autoreactive CD4+ T cells can recognize myelin sheath
proteins, such as myelin basic protein (MBP), myelin-associated
glycoprotein (MAG), and myelin oligodendrocyte glycoprotein (MOG), in
both MS patients and healthy individuals. However,
CD4+ T cells in MS patients exhibit an activated and
memory phenotype with a higher affinity for these proteins compared to
naive myelin-specific CD4+ T cells from healthy controls.
The former understanding of the primary effector cell in EAE and MS was
believed to be Th1, but recently Th17 lymphocytes were shown to induce
other cell types to produce proinflammatory mediators such as IL-6,
GM-CSF, matrix metalloproteases and CXC chemokines, including CXCL8 (a
powerful neutrophil chemoattractant), suggesting that Th17 cells may
contribute to inflammation in the CNS. This is supported by the fact
that the infusion of Th17 cells worsens EAE progression, while the
infusion of Th1 cells does not have a significant effect. Additionally,
an increase in IL-17 transcripts has been observed in chronic MS lesions
compared to acute lesions or healthy individuals, further supporting the
role of Th17 cells in autoimmunity in the brain (Komiyama et al., 2006).
4.3.2. CD8 + T cells in MS
The role of CD8+ T cells in CNS autoimmunity has
recently gained attention, despite the focus of research traditionally
being focused on CD4+ T cells. (Goverman, Perchellet
& Huseby, 2005). Although depleting CD4+ T
lymphocytes in MS patients has not led to improvement, alemtuzumab,
which targets both CD4+ and CD8+ T
cells, has been found to have a positive impact. Further,
CD8+ lymphocytes have been found in MS lesions and CSF
of these patients (Friese & Fugger, 2005). The activity of
CD8+ T cells in the pathology of CNS autoimmunity is
still not well understood, but some studies suggest that they can play
either a beneficial or harmful role. Depletion of CD8+T lymphocytes results in a lower mortality rate in EAE models,
suggesting a regulatory role coinciding with stages of disease
remission. However, specific myelin-reactive CD8+ T
cells have also been reported to be highly pathogenic for the disease,
and infusion of MBP-reactive CD8+ T cells in healthy
animals induces demyelination, clearly demonstrating their role in
pathogenesis (Huseby, Liggitt, Brabb, Schnabel, Ohlen & Goverman,
2001). Further research is needed to fully understand the activity of
CD8+ T cells in CNS autoimmunity and their potential
to regulate or contribute to pathology.