Cross-sectional and longitudinal analysis of myelin-reactive T cells in patients with multiple sclerosis

Journal of Neurology
Jan D LünemannFrauke Zipp

Abstract

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.

Citations

Aug 21, 2013·Trends in Molecular Medicine·Roberto González-AmaroPilar Martín
Oct 30, 2010·Annals of Neurology·Maciej JuryńczykKrzysztof Selmaj
Apr 28, 2009·Autoimmunity Reviews·L Grau-LópezE Martínez-Cáceres
Jan 1, 2007·Expert Review of Clinical Immunology·Claudia J CalderAmit Bar-Or
Oct 1, 2005·Multiple Sclerosis : Clinical and Laboratory Research·D N BourdetteA A Vandenbark
May 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Romina PenitenteFrancesco Ria

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