PMID- 12390966
OWN - NLM
STAT- MEDLINE
DCOM- 20021213
LR  - 20190513
IS  - 0006-8950 (Print)
IS  - 0006-8950 (Linking)
VI  - 125
IP  - Pt 11
DP  - 2002 Nov
TI  - Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: 
      implications for multiple sclerosis therapy. Brain-derived neurotrophic factor.
PG  - 2381-91
AB  - 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.
FAU - Ziemssen, Tjalf
AU  - Ziemssen T
AD  - Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, 
      Germany.
FAU - Kumpfel, Tania
AU  - Kumpfel T
FAU - Klinkert, Wolfgang E F
AU  - Klinkert WE
FAU - Neuhaus, Oliver
AU  - Neuhaus O
FAU - Hohlfeld, Reinhard
AU  - Hohlfeld R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Peptides)
RN  - 5M691HL4BO (Glatiramer Acetate)
SB  - IM
CIN - Brain. 2002 Nov;125(Pt 11):2379-80. PMID: 12390965
MH  - Brain/*immunology
MH  - Brain-Derived Neurotrophic Factor/genetics/*immunology/*metabolism
MH  - Cell Culture Techniques
MH  - Cell Line
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Glatiramer Acetate
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Middle Aged
MH  - Multiple Sclerosis, Relapsing-Remitting/drug therapy/*immunology
MH  - Peptides/therapeutic use
MH  - Phenotype
MH  - Th1 Cells/*immunology
MH  - Th2 Cells/*immunology
MH  - Transcription, Genetic/genetics/immunology
EDAT- 2002/10/23 04:00
MHDA- 2002/12/17 04:00
CRDT- 2002/10/23 04:00
PHST- 2002/10/23 04:00 [pubmed]
PHST- 2002/12/17 04:00 [medline]
PHST- 2002/10/23 04:00 [entrez]
AID - 10.1093/brain/awf252 [doi]
PST - ppublish
SO  - Brain. 2002 Nov;125(Pt 11):2381-91. doi: 10.1093/brain/awf252.