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

Clin Exp Immunol. 2014 Aug;177(2):404-11. doi: 10.1111/cei.12345.

Abstract

T cells with a CD4(+) CD8(+) double-positive (DP) phenotype are present in small numbers in the peripheral blood of healthy humans and may have anti-viral capacities. Here we investigate numbers and function of DP T cells in patients with relapsing-remitting multiple sclerosis (MS), either treatment-naive or under therapy with natalizumab. Flow cytometry analysis revealed that frequencies of circulating DP T cells in treatment-naive and natalizumab-treated MS patients are comparable to healthy controls. These cells have a memory phenotype with cytotoxic potential, express high levels of CD49d and are similarly functional in treatment-naive as well as natalizumab-treated MS patients. DP T cells were enriched in the cerebrospinal fluid, but do not invade acutely inflamed MS lesions. In conclusion, DP T cells are functional in MS and may play a role in the immune surveillance of the central nervous system, but do not display functional impairment under natalizumab therapy.

Keywords: JC virus; cerebrospinal fluid; memory T cells; natalizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, Viral / immunology
  • CD4 Antigens / metabolism*
  • CD8 Antigens / metabolism*
  • Case-Control Studies
  • Cytotoxicity, Immunologic
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • JC Virus / immunology
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / metabolism
  • Natalizumab
  • Phenotype*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antigens, Viral
  • CD4 Antigens
  • CD8 Antigens
  • Natalizumab