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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Myelin-Reactive TCR/IgM Dual-Expresser Lymphocytes in Multiple Sclerosis: Linking Pathogenesis to Anti-CD20 Therapy.

Prajita Paul1, Marjan Behzadirad1, Rafid Al Hallaf1

  • 1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Immunological Investigations
|September 17, 2025
PubMed
Summary

Dual-expressor cells (DEs), a novel lymphocyte population, are found at higher frequencies in multiple sclerosis (MS) patients and respond to myelin antigens. These DEs are depleted by anti-CD20 therapies, offering new insights into MS treatment.

Keywords:
Multiple sclerosisanti-CD20 disease-modifying therapies (DMTs)cerebrospinal fluid (CSF)dual-expresser (DE) lymphocyte

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Area of Science:

  • Immunology
  • Neuroimmunology

Background:

  • Multiple sclerosis (MS) is an autoimmune disease primarily linked to T cells, yet effective treatments target B cells, creating a therapeutic paradox.
  • Dual-expressor cells (DEs), a newly identified lymphocyte population co-expressing T cell receptors (TCRαβ) and B cell receptors (BCRs), are implicated in MS pathogenesis.
  • DEs may represent a crucial link between T and B cell responses in MS and could be unintended targets of anti-CD20 therapies.

Purpose of the Study:

  • To identify and characterize dual-expressor cells (DEs) in patients with relapsing-remitting multiple sclerosis (RRMS).
  • To investigate the role of DEs in MS pathogenesis, including their response to myelin autoantigens.
  • To determine the susceptibility of DEs to anti-CD20 disease-modifying therapies (DMTs).

Main Methods:

  • Analysis of peripheral blood and cerebrospinal fluid (CSF) from RRMS patients and healthy controls.
  • Phenotypic and functional characterization of DEs, including T cell receptor (TCR) and B cell receptor (BCR) expression.
  • Assessment of DE responses to myelin autoantigens and their depletion by ocrelizumab in a pilot cohort.

Main Results:

  • DEs were found at significantly higher frequencies in the peripheral blood and CSF of RRMS patients compared to controls.
  • DEs in CSF showed high CD20 expression (up to 95%) and CXCR3 expression, suggesting involvement in immune cell recruitment.
  • DEs responded robustly to myelin autoantigens and were significantly depleted by ocrelizumab treatment in RRMS patients.

Conclusions:

  • Dual-expressor cells (DEs) are implicated in the pathogenesis of multiple sclerosis (MS).
  • The findings provide a potential explanation for the efficacy of anti-CD20 therapies in MS, a disease traditionally viewed as T cell-driven.
  • DEs represent a novel therapeutic target and a key player in understanding MS immunopathology.