17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain-derived neurotrophic factor.

      Brain
      Brain, immunology, Brain-Derived Neurotrophic Factor, genetics, secretion, Cell Culture Techniques, Cell Line, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Immunosuppressive Agents, therapeutic use, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, drug therapy, Peptides, Phenotype, Th1 Cells, Th2 Cells, Transcription, Genetic

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The clinical effects of glatiramer acetate (GA), an approved therapy for multiple sclerosis, are thought to be largely mediated by a T-helper 1 (TH1) to T-helper 2 (TH2) shift of GA-reactive T-lymphocytes. Current theories propose that activated GA-reactive TH2 cells penetrate the CNS, release anti-inflammatory cytokines such as interleukin (IL)-4, IL-5 and IL-10, and thus inhibit neighbouring inflammatory cells by a mechanism termed 'bystander suppression'. We demonstrate that both GA-specific TH2 and TH1 cells produce the neurotrophin brain-derived neurotrophic factor (BDNF). As the signal-transducing receptor for BDNF, the full-length 145 tyrosine kinase receptor (trk) B, is expressed in multiple sclerosis lesions, it is likely that the BDNF secreted by GA-reactive TH2 and TH1 has neurotrophic effects in the multiple sclerosis target tissue. This may be an additional mechanism of action of GA, and may be relevant for therapies with altered peptide ligands in general. To demonstrate that GA-reactive T cells produce BDNF, we selected four GA-specific, long-term T-cell lines (TCLs), which were characterized according to their cytokine profile by intracellular double-fluorescence flow cytometry. Three TCLs (isolated from a normal subject) had the phenotypes TH1, TH1/TH0, and TH0; the fourth, derived from a GA-treated patient, had the phenotype TH2. To demonstrate BDNF production, we used a combination of RT-PCR (reverse transcription-polymerase chain reaction) and two specially designed techniques for BDNF protein detection: one was based on ELISA (enzyme-linked immunosorbent assay) of supernatants from co-cultures of GA-specific TCLs plus GA-pulsed antigen-presenting cells, and the other on the direct intracellular staining of BDNF in individual T cells and flow cytometric analysis. The different assays and different TCLs yielded similar, consistent results. All four GA-specific T-cell lines, representing the major different TH phenotypes, could be stimulated to produce BDNF.

          Related collections

          Author and article information

          Comments

          Comment on this article