Glatiramer acetate-reactive T cells produce brain-derived neurotrophic factor.
Experimental and MRI evidence suggest that glatiramer acetate's (Copaxone) therapeutic effect in multiple sclerosis (MS) could be mediated by anti-inflammatory GA-reactive Th2 cells that enter the brain, cross-react with myelin antigens, and produce bystander suppression. Furthermore, a neuroprotective effect, possibly mediated by neurotrophic factors such as BDNF, has been suggested based on experimental evidence in animal models, and the observation that inflammatory cells can elaborate BDNF. Therefore, we examined BDNF production in 73 GA, 13 MBP, and 22 TT-reactive short-term T-cell lines from 12 MS patients treated with GA. Ten of 73 GA-TCL (14%), 1 of the MBP-TCL (3%), and 2 of the TT-TCL (9%) produced BDNF levels two standard deviations above the mean levels produced by resting TCL. RT-PCR analysis confirmed BDNF expression in some GA- and MBP-reactive TCL. The mean BDNF level produced by GA-TCL was significantly higher than that for MBP-TCL, or TT-TCL when lines originating from the same patients were compared (P=0.033). All 10 high BDNF-producing GA-reactive TCL were Th2-biased as determined by the IL-5/IFN-gamma levels ratio. A positive correlation was observed between BDNF and IL-5 (Th2 indicator) (P=0.006) but not with IFN-gamma Th1 indicator) levels in GA-TCL derived from MS patients during but not pre-treatment. We conclude that while BDNF production by T cells is not antigen-specific, GA-reactive TCL are more likely to produce BDNF, and to be Th2-biased.
University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Man
M
Chen
Reuben Mari
RM
Valenzuela
Suhayl
S
Dhib-Jalbut
D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D010455:Peptides; D012333:RNA, Messenger; D000068717:Glatiramer Acetate