Longitudinal study of antimyelin T-cell reactivity in relapsing-remitting multiple sclerosis: association with clinical and MRI activity.
In multiple sclerosis (MS), T-cells are considered to be critical in coordinating an immunopathological cascade that results in myelin damage. We investigated whether clinical disease activity or brain inflammatory activity as measured by magnetic resonance imaging (MRI) was associated with changes in autoreactive T-cell reactivities in MS patients. To this end, a longitudinal study was performed in which T-cell-related immune parameters and clinical parameters (including MRI) were monitored in seven relapsing-remitting (RR) MS patients and two healthy controls with bimonthly intervals over a period of 18 months. The serial evaluation of antimyelin (MBP, PLP, MOG) T-cell responses revealed highly dynamic shifts and fluctuations from one pattern to another in a patient-dependent manner. In some of the patients, changes in T-cell-related immune variables were found to concur with MRI activity and generally preceded clinical relapses. These alterations include: increased number of myelin-reactive IFN-gamma secreting T-cells, detection of clonally expanded myelin-reactive T-cells, elevated proinflammatory and decreased antiinflammatory cytokine production, upregulation of ICAM-1 membrane expression and highly increased serum levels of soluble VCAM-1. However, not all exacerbations and MRI changes were associated with changes in antimyelin reactivity. Some of the observed immune alterations were also detected in the healthy controls, indicating that additional regulatory mechanisms-which may be defective in MS-play a role in the downregulation of potentially pathological T-cell responses. In conclusion, this study provides further support for an important role of myelin-reactive T-cells in the pathogenesis of MS. In addition, the observed dynamic changes in the antimyelin T-cell reactivity pattern may be a major obstacle for the development of antigen-specific immunotherapies.
Hellings
Niels
N
Biomedisch Onderzoeksintituut (BIOMED), Limburgs Universitair Centrum, Diepenbeek, Belgium.
Gelin
Geert
G
Medaer
Robert
R
Bruckers
Liesbeth
L
Palmers
Yvan
Y
Raus
Jef
J
Stinissen
Piet
P
D000328:Adult; D015415:Biomarkers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000473:pathology*; D004676:Myelin Basic Protein / Q000276:immunology / Q000494:pharmacology; D009185:Myelin Proteins / Q000276:immunology* / Q000494:pharmacology; D018991:Myelin Proteolipid Protein / Q000276:immunology / Q000494:pharmacology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D015850:Interleukin-6; C571326:MOG protein, human; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma