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| Cell type | Action site | References |
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| CD4 T cells | Activated myelin-reactive CD4+ T cells are present in the blood and cerebrospinal fluid (CSF) of MS patients. Found predominating in acute lesions (perivascular infiltrates) | [47, 59–66] |
| B cells | Located in the meninges and in the large perivascular spaces around the cerebral ventricles. While CD20+ B lymphocytes predominate and may have pro-inflammatory properties in early and active lesions, the number of plasma cells with potential anti-inflammatory properties increases in later stages | [67–80] |
| Macrophages | Major effectors of inflammation and demyelination in both MS and EAE found in MS lesions | [7, 48, 58, 81–89] |
| Myeloid | Aberrant myeloid function is often observed in MS plaques in the CNS | [48, 90, 91] |
| Microglia/macrophages | Shift in M1/M2 balance is important for disease pregression.
Early phase: immediate activation to become classically activated macrophages (M1 cells), releasing pro-inflammatory cytokines and damaging CNS tissue.
Later phase, microglia/macrophages in the inflamed CNS are less activated, present as alternatively activated macrophage phenotype (M2 cells), releasing anti-inflammatory cytokines, accompanied by inflammation resolution and tissue repair | [58, 83, 85, 86, 92–96] |
| CD8 T cells | Frequently found in chronic lesions (perivascular infiltrates) | [48, 63, 66] |
| Tregs | In CSF, they appear to be defective and dysregulation of suppressive and migratory markers on Tregs into CNS has been linked to MS | [97–100] |
| Dendritic cells (DCs) | Found to be increased in the brain parenchyma and myelin-reactive T cells require the involvement of CNS microvessel-associated DCs to recognize the local antigen | [101–105] |
| Neutrophils | In MS patients, neutrophils have been identified in the cerebral fluid, and also postmortem CNS material demonstrated neutrophil infiltration in areas where the BBB was leaking | [106–112] |
| Natural killer cells | NK cells are seen in the CSF of MS patients and despite having a low absolute number, they are highly active cytotoxin molecules that can kill autologous activated immune cells as well as other stressed cells | [113–118] |
| Mast cells | Mast cells (MCs), which produce histamine and are present before any pathological or clinical symptoms of MS, are found in the thalamus and hypothalamus of the brain | [119–121] |
| Astrocytes | Astrocytes become active in demyelinating lesions. They had noticeably higher levels of natural cytotoxicity triggering receptor 1 (NCR1) expression in MS white matter lesions. During demyelination, astrocytes generate significant quantities of matrix metalloproteinases (MMPs), that aid tissue damage and reorganization, and produce gliotic scars in inactive lesions and help maintain the BBB and the blood-spinal cord barrier, as well as remyelination and neuronal integrity | [122–129] |
| γδ T cells | γδ T cells have been identified in greater numbers in MS white matter plaques and cerebral fluid, causing harm to oligodendrocytes and contributing to CNS demyelination and fibrosis | [130–133] |
| Natural killer T (NKT) cells | NKT cells may proliferate in MS patients’ CSF as a response to the disease’s immunological reactivity in the CNS | [115, 134] |
| Mucosal-associated invariant T (MAIT) cells | The proportion of MAIT cells in the CSF of MS patients was considerably greater than in peripheral blood in paired samples, indicating that MAIT cells can cross the BBB | [135–138] |
| Innate-like B (ILB) cells | CD5+ (innate) B cells are a provider of persistent antilipid IgM antibodies, which can be observed in the CSF as a portion of the oligoclonal IgM bands | [139, 140] |
| Innate lymphoid cells (ILC) | In EAE, ILC subtypes can invade the CNS and remain in the meninges. They release cytokines that control T-cell inflammation as well as pro-inflammatory cytokines that worsen the immune response in MS | [141, 142] |
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