Cytokine profile of myelin basic protein-reactive T cells in multiple sclerosis and healthy individuals.
Myelin basic protein (MBP)-reactive T cells have been implicated in the autoimmune pathogenesis of multiple sclerosis (MS). In this study, we examined the cytokine profile of 531 primary MBP-reactive T-cell lines and 72 independently established clones from 32 patients with MS and 18 healthy controls (NS) by using highly sensitive enzyme-linked immunosorbent assays. An increased number of primary T-cell lines producing interferon-gamma (IFN gamma) and/or interleukin-4 (IL-4) in response to MBP were found in patients with MS compared with controls. No distinct Th1 or Th2 subtypes could be demonstrated among the MBP-reactive clones. IL-4 was more frequently observed among MS-derived clones. Clones derived from MS patients produced increased levels of IL-2, IL-4, tumor necrosis factor-alpha (TNF alpha), IFN gamma, and IL-10, but not IL-6. It is interesting that MBP-reactive T cells from MS patients expressing the disease-associated HLA-DRB1*15 allele produced increased quantities of TNF alpha, a cytokine suggested to play an important role in inflammation and demyelination. When challenged with either MBP or a bacterial superantigen, the clones expressed similar levels of the proinflammatory cytokine IFN gamma. Our study suggests a functional difference in T-cell responses to MBP in patients with MS compared with healthy individuals, and provides further insights into the role of MBP-reactive T cells and their cytokine profile in the inflammatory processes of MS.
Hermans
G
G
Multiple Sclerosis Research Unit, Dr L. Willems-Instituut and Limburgs Universitair Centrum, Diepenbeek, Belgium.
Stinissen
P
P
Hauben
L
L
Van den Berg-Loonen
E
E
Raus
J
J
Zhang
J
J
D000328:Adult; D002460:Cell Line; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000494:pharmacology*; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
D016207:Cytokines; D004768:Enterotoxins; D006680:HLA Antigens; D004676:Myelin Basic Protein; C031818:enterotoxin B, staphylococcal