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.