Multiple sclerosis: glatiramer acetate induces anti-inflammatory T cells in the cerebrospinal fluid.
Glatiramer acetate (GA) is believed to induce GA-reactive T cells that secrete anti-inflammatory cytokines at the site of inflammation in multiple sclerosis (MS). However, GA-reactive T cells have not been established from the intrathecal compartment of MS patients, and intrathecal T cells may differ from T cells in blood. Here, we compared the phenotype of GA-reactive T cells from the cerebrospinal fluid (CSF) and blood of five MS patients treated with GA for 3-36 months, and in three of these patients also before treatment. From the CSF of these patients, all 22 T cell lines generated before and all 38 T cell lines generated during treatment were GA-reactive. GA treatment induced a more pronounced anti-inflammatory profile of GA-reactive T cell lines from CSF than from blood. While GA-reactive T cell clones from CSF were restricted by either human leukocyte antigen (HLA) -DR or HLA-DP, only HLA-DR restricted GA-reactive T cell clones were detected in blood. No cross reactivity with myelin proteins was detected in GA-reactive T cell lines or clones from CSF. These results suggest that a selected subset of GA-reactive T cells are present in the intrathecal compartment, and support an anti-inflammatory mechanism of action for GA.
Hestvik
A L K
AL
Faculty of Medicine, Institute of Immunology, Rikshospitalet-Radiumhospitalet, Oslo, Norway. a.l.k.hestvik@medisin.uio.no
Skorstad
G
G
Price
D A
DA
Vartdal
F
F
Holmoy
T
T
D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D000068717:Glatiramer Acetate; D006682:HLA-DP Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D016207:Cytokines; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D009185:Myelin Proteins; D010455:Peptides; D000068717:Glatiramer Acetate