English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Glatiramer acetate-specific T-helper 1-and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy

Ziemssen, T., Kümpfel, T., Klinkert, W. E. F., Neuhaus, O., & Hohlfeld, R. (2002). Glatiramer acetate-specific T-helper 1-and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain, 125, 2381-2391.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Ziemssen, T.1, Author           
Kümpfel, T.1, Author           
Klinkert, W. E. F.1, Author           
Neuhaus, O.1, Author           
Hohlfeld, R.1, Author           
Affiliations:
1Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              

Content

show
hide
Free keywords: multiple sclerosis; altered peptide ligand (APL); immunotherapy; neuroprotection; glatiramer acetate
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2002-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 10456
ISI: 000178834400002
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Brain
  Alternative Title : Brain
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 125 Sequence Number: - Start / End Page: 2381 - 2391 Identifier: ISSN: 0006-8950