title: Secretion of brain-derived neurotrophic factor by glatiramer acetate-reactive T-helper cell lines: Implications for multiple sclerosis therapy.
abstract: Treatment with glatiramer acetate (GA) is thought to induce an in vivo change of the cytokine secretion pattern and the effector function of GA-reactive T helper (TH) cells (TH1-TH2-shift). Current theories propose that GA-reactive TH2 cells can penetrate the CNS, since they are activated by daily immunization. Inside the CNS, GA-reactive T cells may cross-react with products of the local myelin turnover presented by local antigen-presenting cells (APCs). Thus, some of the GA-specific TH2 cells may be stimulated to release anti-inflammatory cytokines inhibiting neighbouring inflammatory cells by a mechanism called bystander suppression. We demonstrate that both GA-specific TH2 and TH1 cells produce the neurotrophin brain-derived neurotrophic factor (BDNF). To demonstrate that GA-reactive T cells produce BDNF, we analyzed GA-specific, long-term T-cell lines (TCLs) and used a combination of reverse-transcription PCR and two specially designed techniques for BDNF protein detection: one was based on ELISA 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 GA-specific TH1, TH2 and TH0 lines could be stimulated to produce BDNF.
authors.affiliation: Neuroimmunological lab, Neurological University Clinic, Dresden, Germany. Ziemssen@web.de
authors.forename: Tjalf
authors.initials: T
authors.lastname: Ziemssen
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel
authors.forename: Hauke
authors.initials: H
authors.lastname: Schneider
authors.forename: Wolfgang E F
authors.initials: WE
authors.lastname: Klinkert
authors.forename: Oliver
authors.initials: O
authors.lastname: Neuhaus
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
mesh_terms: D015152:Blotting, Northern / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018418:Th2 Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007166:Immunosuppressive Agents; D010455:Peptides; D012333:RNA, Messenger; D000068717:Glatiramer Acetate