title: T-cell reactivity to multiple myelin antigens in multiple sclerosis patients and healthy controls.
abstract: Myelin proteins, including myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) are candidate autoantigens in MS. It is not clear whether MS patients show a predominant reactivity to one or several myelin antigens. We evaluated the IFN-gamma production induced by MBP and MOG and selected MBP-, MOG- and PLP-peptides in MS patients and healthy controls using the IFN-gamma ELISPOT assay. Most MS patients and healthy controls showed a heterogeneous anti-myelin T-cell reactivity. Interestingly in MS patients a positive correlation was found between the anti-MOG and anti-MBP T-cell responses. No myelin peptide was preferentially recognized among the peptides tested (MBP 84-102, 143-168, MOG 1-22, 34-56, 64-86, 74-96, PLP 41-58, 184-199, 190-209). In addition the frequency of IL2R+ MBP reactive T-cells was significantly increased in blood of MS patients as compared with healthy subjects, indicating that MBP reactive T-cells exist in an in vivo activated state in MS patients. Most of the anti-MBP T-cells were of the Th1-type because reactivity was observed in IFN-gamma but not in IL-4 ELISPOT-assays. Using Th1 (IL-12) and Th2 (IL-4) promoting conditions we observed that the cytokine secretion pattern of anti-MBP T-cells still is susceptible to alteration. Our data further indicate that precursor frequency analysis of myelin reactive T-cells by proliferation-based assays may underestimate the true frequency of myelin specific T-cells significantly.
authors.affiliation: Biomedisch Onderzoeksintituut DWI, Limburgs Universitair Centrum, Diepenbeek, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Hellings
authors.forename: M
authors.initials: M
authors.lastname: Barée
authors.forename: C
authors.initials: C
authors.lastname: Verhoeven
authors.forename: M B
authors.initials: MB
authors.lastname: D'hooghe
authors.forename: R
authors.initials: R
authors.lastname: Medaer
authors.forename: C C
authors.initials: CC
authors.lastname: Bernard
authors.forename: J
authors.initials: J
authors.lastname: Raus
authors.forename: P
authors.initials: P
authors.lastname: Stinissen
mesh_terms: D000328:Adult; D000941:Antigens / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000097:blood / Q000276:immunology; D009185:Myelin Proteins / Q000097:blood / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000097:blood / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000097:blood / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000941:Antigens; D007376:Interleukin-2; C571326:MOG protein, human; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma