Programmed Cell Death Protein 1–Positive CD8
            <sup>+</sup>
            T Cells in Multiple Sclerosis

Smolders, Joost; Hamann, Jörg

doi:10.1212/nxi.0000000000001173

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…In line with these findings, in early MS brain lesions the majority of CD8+ T lymphocytes express CD69, but not CD103, and were shown to contain granzyme B (12). Although a link has been suggested between T cell exhaustion and the progression of chronic neuroinflammation in MS, the contribution of T EX CD8+ T lymphocytes in MS course is unclear (149). EBV infection is now considered a key environmental factor for chronic CNS inflammation during MS and CD8+ T cells are clonally expanded against EBV-derived antigens presented by B cells in MS patients (12).…”

Section: Multiple Sclerosismentioning

confidence: 80%

The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders

2023

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CD8+ lymphocytes are adaptive immunity cells with the particular function to directly kill the target cell following antigen recognition in the context of MHC class I. In addition, CD8+ T cells may release pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and a plethora of other cytokines and chemoattractants modulating immune and inflammatory responses. A role for CD8+ T cells has been suggested in aging and several diseases of the central nervous system (CNS), including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, limbic encephalitis-induced temporal lobe epilepsy and Susac syndrome. Here we discuss the phenotypic and functional alterations of CD8+ T cell compartment during these conditions, highlighting similarities and differences between CNS disorders. Particularly, we describe the pathological changes in CD8+ T cell memory phenotypes emphasizing the role of senescence and exhaustion in promoting neuroinflammation and neurodegeneration. We also discuss the relevance of trafficking molecules such as selectins, mucins and integrins controlling the extravasation of CD8+ T cells into the CNS and promoting disease development. Finally, we discuss how CD8+ T cells may induce CNS tissue damage leading to neurodegeneration and suggest that targeting detrimental CD8+ T cells functions may have therapeutic effect in CNS disorders.

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Section: Multiple Sclerosismentioning

confidence: 80%

The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders

2023

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“…However, in MS, the differentiation process is some-how imperfect, and chronic inflammation persists, potentially leading to neuropathy. In fact, in the group of MS patients with good steroid treatment responsiveness, the number of PD-1-positive T cells in the cerebrospinal fluid was high, and conversely, the PD-1positive rate decreased in the group with residual symptoms of neuropathy even after treatment [85]. Thus, MS and neuromyelitis optica both have autoimmune conditions in their backgrounds, and the restoration of weakened immune regulatory functions may be a true disease-modifying treatment.…”

Section: Discussionmentioning

confidence: 98%

“…Regarding the relationship between the inhibitory immune-receptor PD-1, which is known as a checkpoint of immune regulation, and the pathology of MS among CD8positive T cells in the peripheral blood, the proportion of PD-1-positive cells is decreased in MS patients compared with healthy controls and is restored by interferon-β (IFNβ) treatment [82][83][84][85][86]. In addition, in the cerebrospinal fluid during inflammatory attacks, patients with a high proportion of PD-1+ CD8+ T cells respond better to acute treatment and are more likely to recover to their original level of neuropathy than those with a low proportion [75,87,88].…”

Section: Programmed Death Receptor-1 (Pd-1)-positive Cells In Ms Pati...mentioning

confidence: 99%

Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells

Matsuzaka,

Yashiro

2023

Biologics

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, characterized by multiple lesions occurring temporally and spatially. Additionally, MS is a disease that predominates in the white population. In recent years, there has been a rapid increase in the number of patients, and it often occurs in young people, with an average age of onset of around 30 years old, but it can also occur in children and the elderly. It is more common in women than men, with a male-to-female ratio of approximately 1:3. As the immunopathogenesis of MS, a group of B cells called plasmablasts controls encephalomyelitis via IL-10 production. These IL-10-producing B cells, called regulatory B cells, suppress inflammatory responses in experimental mouse models of autoimmune diseases including MS. Since it has been clarified that these regulatory B cells are plasmablasts, it is expected that the artificial control of plasmablast differentiation will lead to the development of new treatments for MS. Among CD8-positive T cells in the peripheral blood, the proportion of PD-1-positive cells is decreased in MS patients compared with healthy controls. The dysfunction of inhibitory receptors expressed on T cells is known to be the core of MS immunopathology and may be the cause of chronic persistent inflammation. The PD-1+ CD8+ T cells may also serve as indicators that reflect the condition of each patient in other immunological neurological diseases such as MS. Th17 cells also regulate the development of various autoimmune diseases, including MS. Thus, the restoration of weakened immune regulatory functions may be a true disease-modifying treatment. So far, steroids and immunosuppressants have been the mainstream for autoimmune diseases, but the problem is that this kills not only pathogenic T cells, but also lymphocytes, which are necessary for the body. From this understanding of the immune regulation of MS, we can expect the development of therapeutic strategies that target only pathogenic immune cells.

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Machine learning-driven diagnosis of multiple sclerosis from whole blood transcriptomics

Omrani,

Chiarelli,

Acquaviva

et al. 2024

Brain, Behavior, and Immunity

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Programmed Cell Death Protein 1–Positive CD8 ⁺ T Cells in Multiple Sclerosis

Cited by 5 publications

References 20 publications

The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders

The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders

Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells

Machine learning-driven diagnosis of multiple sclerosis from whole blood transcriptomics

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Programmed Cell Death Protein 1–Positive CD8 + T Cells in Multiple Sclerosis

Cited by 5 publications

References 20 publications

The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders

The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders

Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells

Machine learning-driven diagnosis of multiple sclerosis from whole blood transcriptomics

Contact Info

Product

Resources

About

Programmed Cell Death Protein 1–Positive CD8 ⁺ T Cells in Multiple Sclerosis