Proinflammatory CD20+ T cells in the pathogenesis of multiple sclerosis

Essen, Marina Rode von; Ammitzbøll, Cecilie; Hansen, Rasmus Hvass; Petersen, Eva Rosa; McWilliam, Oskar; Marquart, Hanne Vibeke; Damm, Peter; Sellebjerg, Finn

doi:10.1093/brain/awy301

Cited by 85 publications

(150 citation statements)

References 34 publications

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“…This represented a substantial enrichment in CD20 expression in comparison to the total frequency of CD20 + CD8 + T cells (5.5 ± 0.7% in MS patients; 4.4 ± 0.8% in controls). Influenza-specific CD20 + CD8 + T cell populations exhibited a predominantly memory phenotype, consistent with the known activated state of CD20 + T cells (35,36). The memory status of CD20-expressing myelin-specific CD8 + T cells was variable, but with an overall significant increase in myelin-specific memory CD20 + CD8 + T cells in MS patients (53.7 ± 10.3%) compared to control subjects (27.0 ± 9.7%) (SI Appendix, Fig.…”

Section: Resultssupporting

confidence: 69%

“…Although typically associated with B cells, CD20 is also expressed on a subset of highly activated proinflammatory T cells and is typically found in memory T cell populations (35,36,42). CD20 + T cells are reported to be increased in MS patients (35,36), are present in MS lesions (43), and are reduced by anti-CD20 mAb therapies (35,42,44). The expression of CD20 was therefore measured on ex vivo antigen-specific CD8 + T cells (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Although CD20 is a hallmark cell surface molecule expressed by B cells and is the target for B cell-depleting therapy in MS, it is now recognized that some T cells express CD20, which is expressed by a higher proportion of CD8 + T cells compared to CD4 + T cells (35,36,42,51). CD8 + T cells expressing CD20 have been previously demonstrated to be highly activated proinflammatory cytokine-producing memory T cells bearing CNS-homing chemokine receptors and adhesion molecules (36,42), thus highlighting their pathogenic potential. In addition, CD20 + T cells have been directly implicated in MS pathogenesis (35,36,43).…”

Section: Discussionmentioning

confidence: 99%

“…CD8 + T cells expressing CD20 have been previously demonstrated to be highly activated proinflammatory cytokine-producing memory T cells bearing CNS-homing chemokine receptors and adhesion molecules (36,42), thus highlighting their pathogenic potential. In addition, CD20 + T cells have been directly implicated in MS pathogenesis (35,36,43). The precise mechanism(s) responsible for the benefit of anti-CD20 mAb in MS is not entirely clear and may include effects on T cells (52,53).…”

Section: Discussionmentioning

confidence: 99%

“…This activated phenotype was reversible as the memory and CD20-expressing populations of certain myelin-specific CD8 + T cells were reduced following anti-CD20 treatment. monoclonal antibody (mAb) treatment (35,36). Interestingly, memory myelin-specific CD8 + T cells were increased in MS patients compared to controls, indicating prior exposure to antigen.…”

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confidence: 99%

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Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

Sabatino

Wilson

Calabresi³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

103

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CD8 + T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8 + T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8 + T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8 + T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8 + T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramerpositive myelin-specific CD8 + T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8 + T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8 + T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20 + CD8 + T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8 + T cells in MS, indicates these cells may be attractive targets in MS therapy. multiple sclerosis | CD8 + T cells | myelin antigen | anti-CD20 therapy

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Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

Sabatino

Wilson

Calabresi³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

103

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CD11c⁺ B cells in relapsing–remitting multiple sclerosis and effects of anti‐CD20 therapy

El Mahdaoui,

Hansen,

von Essen

et al. 2024

Ann Clin Transl Neurol

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ObjectivesB cells are important in the pathogenesis of multiple sclerosis. It is yet unknown which subsets may be involved, but atypical B cells have been proposed as mediators of autoimmunity. In this study, we investigated differences in B‐cell subsets between controls and patients with untreated and anti‐CD20‐treated multiple sclerosis.MethodsWe recruited 155 participants for an exploratory cohort comprising peripheral blood and cerebrospinal fluid, and a validation cohort comprising peripheral blood. Flow cytometry was used to characterize B‐cell phenotypes and effector functions of CD11c+ atypical B cells.ResultsThere were no differences in circulating B cells between controls and untreated multiple sclerosis. As expected, anti‐CD20‐treated patients had a markedly lower B‐cell count. Of B cells remaining after treatment, we observed higher proportions of CD11c+ B cells and plasmablasts. CD11c+ B cells were expanded in cerebrospinal fluid compared to peripheral blood in controls and untreated multiple sclerosis. Surprisingly, the proportion of CD11c+ cerebrospinal fluid B cells was higher in controls and after anti‐CD20 therapy than in untreated multiple sclerosis. Apart from the presence of plasmablasts, the cerebrospinal fluid B‐cell composition after anti‐CD20 therapy resembled that of controls. CD11c+ B cells demonstrated a high potential for both proinflammatory and regulatory cytokine production.InterpretationThe study demonstrates that CD11c+ B cells and plasmablasts are less efficiently depleted by anti‐CD20 therapy, and that CD11c+ B cells comprise a phenotypically and functionally distinct, albeit heterogenous, B‐cell subset with the capacity of exerting both proinflammatory and regulatory functions.

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CD20⁺ T Cells as Pathogenic Players and Therapeutic Targets in MS

Meinl

Hohlfeld

2021

Annals of Neurology

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Proinflammatory CD20+ T cells in the pathogenesis of multiple sclerosis

Cited by 85 publications

References 34 publications

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

CD11c⁺ B cells in relapsing–remitting multiple sclerosis and effects of anti‐CD20 therapy

CD20⁺ T Cells as Pathogenic Players and Therapeutic Targets in MS

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Proinflammatory CD20+ T cells in the pathogenesis of multiple sclerosis

Cited by 85 publications

References 34 publications

Anti-CD20 therapy depletes activated myelin-specific CD8+T cells in multiple sclerosis

Anti-CD20 therapy depletes activated myelin-specific CD8+T cells in multiple sclerosis

CD11c+ B cells in relapsing–remitting multiple sclerosis and effects of anti‐CD20 therapy

CD20+ T Cells as Pathogenic Players and Therapeutic Targets in MS

Contact Info

Product

Resources

About

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

CD11c⁺ B cells in relapsing–remitting multiple sclerosis and effects of anti‐CD20 therapy

CD20⁺ T Cells as Pathogenic Players and Therapeutic Targets in MS