Cross-sectional and longitudinal analysis of myelin-reactive T cells in patients with multiple sclerosis.
Activated myelin-specific T cells are thought to mediate inflammatory tissue damage in multiple sclerosis (MS). Applying a large panel of myelin antigens, we demonstrate the direct ex vivo detection of viable IFN-gamma/TNF-alpha producing CD4+/CD69+ T cells 6 hours after antigenic challenge, by intracellular flow cytometry in 3/33 MS patients and 2/26 healthy controls with calculated frequencies of (mean +/- SEM): 0.031% +/- 0.002% versus 0.037% +/- 0.029%. By comparison, the recently developed IL-7 modified proliferation assay revealed i) a higher number of individuals showing myelin reactivity (17/37 MS patients and 12/24 healthy individuals) and ii) a significant difference in the response to myelin basic protein (MBP) between the two groups in a longitudinal analysis, indicating a higher activity of myelin-specific T cells in MS patients. Our data provide new perspectives in detecting pathogenetically relevant T cells, but clearly demonstrate the different conclusions which must be drawn from various approaches concerning the quantification of autoreactive T cells.
Lünemann
Jan D
JD
Institute of Neuroimmunology, Neuroscience Research Center, Charité, 10098, Berlin, Germany.
Rückert
Sandra
S
Kern
Florian
F
Wendling
Uwe
U
van der Zee
Ruud
R
Volk
Hans D
HD
Zipp
Frauke
F
D000328:Adult; D000595:Amino Acid Sequence; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology*; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D004676:Myelin Basic Protein