Role of CD4+ T Cells in the Pathophysiology of Multiple Sclerosis

Sato, Fumitaka; Omura, Seiichi; Jaffe, Stephen L.; Tsunoda, Ikuo

doi:10.1016/b978-0-12-800763-1.00004-x

Cited by 11 publications

(10 citation statements)

References 155 publications

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“…The spectrum of T helper (Th)1 and Th2 subsets has now been expanded to include Th17 effector T cells and FoxP3 + regulatory T cells (Treg) subsets, as well as the lesser studied Tfh, Th9, and Th22 cells [ 154 ]. Subpopulations of differentiated CD4 + T cells show a high degree of plasticity [ 155 ] and although some subsets seem to be fairly stable, some flexibility permits transitions between them and the creation of hybrid transition forms [ 156 ].…”

Section: T Cellsmentioning

confidence: 99%

The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis

Sarkar,

Willson,

Jordan

2024

Journal of Immunology Research

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Multiple sclerosis (MS) is a neurodegenerative autoimmune disease characterized by the destruction of the myelin sheath of the neuronal axon in the central nervous system. Many risk factors, including environmental, epigenetic, genetic, and lifestyle factors, are responsible for the development of MS. It has long been thought that only adaptive immune cells, especially autoreactive T cells, are responsible for the pathophysiology; however, recent evidence has indicated that innate immune cells are also highly involved in disease initiation and progression. Here, we compile the available data regarding the role immune cells play in MS, drawn from both human and animal research. While T and B lymphocytes, chiefly enhance MS pathology, regulatory T cells (Tregs) may serve a more protective role, as can B cells, depending on context and location. Cells chiefly involved in innate immunity, including macrophages, microglia, astrocytes, dendritic cells, natural killer (NK) cells, eosinophils, and mast cells, play varied roles. In addition, there is evidence regarding the involvement of innate-like immune cells, such as γδ T cells, NKT cells, MAIT cells, and innate-like B cells as crucial contributors to MS pathophysiology. It is unclear which of these cell subsets are involved in the onset or progression of disease or in protective mechanisms due to their plastic nature, which can change their properties and functions depending on microenvironmental exposure and the response of neural networks in damage control. This highlights the need for a multipronged approach, combining stringently designed clinical data with carefully controlled in vitro and in vivo research findings, to identify the underlying mechanisms so that more effective therapeutics can be developed.

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Section: T Cellsmentioning

confidence: 99%

The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis

Sarkar,

Willson,

Jordan

2024

Journal of Immunology Research

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“…Second, although both MS and AD have often been described as CNS diseases with “neuroinflammation”, 134 substantial perivascular T cell infiltration is seen in MS, but not in AD. While microglia and astrocytes (resident innate cells) are activated in both MS and AD, pro-inflammatory peripheral cellular immune responses, particularly Th1 and Th17 cells, contribute to the pathogenesis only in MS.…”

Section: Helicobacter Pylori Infection In Ms and Admentioning

confidence: 99%

Helicobacter pylori and gut microbiota in multiple sclerosis versus Alzheimer's disease: 10 pitfalls of microbiome studies

Park

Omura

Fujita

et al. 2017

Clinical & Exp Neuroim

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Alteration of microbiota has been associated with intestinal, inflammatory, and neurological diseases. Abundance of “good bacteria” such as Bifidobacterium, or their products have been generally believed to be beneficial for any diseases, while “bad bacteria” such as pathogenic Helicobacter pylori are assumed to be always detrimental for hosts. However, this is not the case when we compare and contrast the association of the gut microbiota with two neurological diseases, multiple sclerosis (MS) and Alzheimer’s disease (AD). Following H. pylori infection, pro-inflammatory T helper (Th)1 and Th17 immune response are initially induced to eradicate bacteria. However, H. pylori evades the host immune response by inducing Th2 cells and regulatory T cells (Tregs) that produce anti-inflammatory interleukin (IL)-10. Suppression of anti-bacterial Th1/Th17 cells by Tregs may enhance gastric H. pylori propagation, followed by a cascade reaction involving vitamin B12 and folic acid malabsorption, plasma homocysteine elevation, and reactive oxygen species induction. This can damage the blood-brain barrier (BBB), leading to accumulation of amyloid-β in the brain, a hallmark of AD. On the other hand, this suppression of pro-inflammatory Th1/Th17 responses to H. pylori has protective effects on the hosts, since it prevents uncontrolled gastritis as well as suppresses the induction of encephalitogenic Th1/Th17 cells, which can mediate neuroinflammation in MS. The above scenario may explain why chronic H. pylori infection is positively associated with AD, while it is negatively associated with MS. Lastly, we list “10 pitfalls of microbiota studies”, which will be useful for evaluating and designing clinical and experimental microbiota studies.

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“…Although the precise etiology of MS is unknown, MS is believed to be an immune‐mediated disease, occurring in genetically susceptible individuals, precipitated by one or more environmental agents, particularly viruses, including Epstein‐Barr virus (human herpesvirus [HHV]‐4), HHV‐6, measles virus and retroviruses . CD4 + T helper (Th) cells have been proposed to play a key role in MS pathogenesis . CD4 + T cells can be divided into four subsets, Th1, Th2, Th17 and regulatory T cells (Tregs), based on their cytokine production: Th1 cells, interferon (IFN)‐γ and interleukin (IL)‐2; Th2 cells, IL‐4, IL‐5 and IL‐13; Th17 cells, IL‐17, IL‐21 and IL‐22; and Tregs, transforming growth factor (TGF)‐β and IL‐10 (Fig.…”

Section: Tmev‐induced Demyelinating Diseasementioning

confidence: 99%

Three immune‐mediated disease models induced by Theiler's virus: Multiple sclerosis, seizures and myocarditis

Tsunoda

Sato

Omura

et al. 2016

Clinical & Exp Neuroim

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Theiler’s murine encephalomyelitis virus (TMEV) infection has been used as a viral model for multiple sclerosis (MS), as TMEV can induce chronic inflammatory demyelinating lesions with viral persistence in the spinal cord of SJL/J mice. In contrast, when C57BL/6 mice are infected with TMEV, the mice can clear the virus from the central nervous system (CNS), without viral persistence or demyelination, but develop seizures and hippocampal sclerosis, which has been used as a viral model for seizures/epilepsy. In the two TMEV-induced CNS disease models, not only viral infection, but also immune responses contribute to the pathogenesis. Interestingly, acquired immunity plays an effector role in the MS model, whereas innate immunity appears to contribute to the development of seizures. Recently, we have established the third TMEV-induced disease model, a mouse model for viral myocarditis, using C3H mice. TMEV-induced myocarditis is a triphasic disease, which mimics human myocarditis; phase I, mediated by viral replication in the heart and innate immunity; phase II, mediated by acquired immunity; and phase III, resulted from cardiac fibrosis. The genetic susceptibility to the aforementioned three models (MS, seizures and myocarditis) differs among mouse strains. We have compared and contrasted the three models induced by one single pathogen, TMEV, particularly in regard to the roles of T helper cells and natural killer T cells, which will give an insight into how interactions between the immune system and the host’s genetic background determine the tissue tropism of virus and the development of virus-induced organ-specific immunopathology.

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Role of CD4+ T Cells in the Pathophysiology of Multiple Sclerosis

Cited by 11 publications

References 155 publications

The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis

The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis

Helicobacter pylori and gut microbiota in multiple sclerosis versus Alzheimer's disease: 10 pitfalls of microbiome studies

Three immune‐mediated disease models induced by Theiler's virus: Multiple sclerosis, seizures and myocarditis

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