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

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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-γ/TNF-α 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.

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Authors and Affiliations

  1. Institute of Neuroimmunology, Neuroscience Research Center, Charité, 10098, Berlin, Germany

    Jan D. Lünemann*, Sandra Rückert*, Uwe Wendling &  Frauke Zipp MD

  2. Dept. of Medical Immunology, Charité, Berlin, Germany

    Florian Kern & Hans D. Volk

  3. Dept. of Infectious Diseases & Immunology Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

    Ruud van der Zee

Authors
  1. Jan D. Lünemann*
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  2. Sandra Rückert*
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  3. Florian Kern
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  4. Uwe Wendling
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  5. Ruud van der Zee
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  6. Hans D. Volk
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  7. Frauke Zipp MD
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Correspondence to Frauke Zipp MD.

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* both authors contributed equally

This work was supported by grants from the Gemeinnützige Hertie-Stiftung, the Charité Sonderforschungsbereich 507 (F. Zipp, SFB 507), and the BMBF.

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Lünemann*, J.D., Rückert*, S., Kern, F. et al. Cross-sectional and longitudinal analysis of myelin-reactive T cells in patients with multiple sclerosis. J Neurol 251, 1111–1120 (2004). https://doi.org/10.1007/s00415-004-0493-1

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  • DOI: https://doi.org/10.1007/s00415-004-0493-1

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