Analysis of CD4+ CD8+ double-positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions

A Waschbisch1, L Sammet, S Schröder

  • 1Department of Neurology, Friedrich-Alexander University of Erlangen, Erlangen, Germany.

Insights

Double-positive (DP) T cells are functional in multiple sclerosis (MS) patients, with numbers and activity comparable to healthy individuals. These cells, found in cerebrospinal fluid, show no functional impairment under natalizumab therapy.

Area of Science:

  • Immunology
  • Neuroimmunology
  • Cellular Immunology

Background:

  • CD4(+) CD8(+) double-positive (DP) T cells are rare in human peripheral blood and possess potential anti-viral functions.
  • Understanding DP T cell behavior in autoimmune diseases like multiple sclerosis (MS) is crucial for immune surveillance insights.

Purpose of the Study:

  • To investigate the numbers and function of DP T cells in patients with relapsing-remitting multiple sclerosis (MS).
  • To compare DP T cells in treatment-naive MS patients and those undergoing natalizumab therapy with healthy controls.

Main Methods:

  • Flow cytometry was used to analyze circulating DP T cell frequencies.
  • Functional characteristics, including cytotoxic potential and CD49d expression, were assessed.
  • DP T cell presence in cerebrospinal fluid and inflamed MS lesions was examined.

Main Results:

  • Frequencies of circulating DP T cells in MS patients (treatment-naive and natalizumab-treated) were similar to healthy controls.
  • DP T cells exhibit a memory phenotype, express high CD49d levels, and possess cytotoxic potential.
  • These cells were enriched in cerebrospinal fluid but did not infiltrate acutely inflamed MS lesions.

Conclusions:

  • DP T cells are functional in the context of MS and may contribute to central nervous system immune surveillance.
  • Natalizumab therapy does not impair the function of DP T cells in MS patients.
  • DP T cells represent a potentially important cellular component in the neuroimmune landscape of MS.

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