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The Journal of Immunology, 2004, 173: 2896.
Copyright © 2004 by The American Association of Immunologists


LETTERS TO THE EDITOR

MBP-Induced Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice

Ralf A. Linker and Ralf Gold

Institute for Multiple Sclerosis Research, University of Goettingen and Gemeinnuetzige Hertie-Stiftung, Goettingen, Germany

We followed with great interest the "Cutting Edge" contribution by Faunce et al. (1) reporting bovine myelin basic protein (MBP) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. In response, Furlan (2) noted that C57BL/6 (H2b) mice are traditionally considered resistant to MBP-EAE induced by standard immunization protocols.

We have recently been able to induce MBP-EAE in C57BL/6 mice using rat MBP and a boost protocol, in which mice were immunized s.c. with 200 µg rat MBP in CFA on days 0 and 17 followed by standard pertussis toxin (3). This protocol results in a monophasic, moderate disease course starting around day 20 with the histopathological hallmarks of inflammation and axonal damage, but no significant demyelination. In our hands, immunization with guinea pig or murine MBP instead of rat MBP was not successful.

Other known protocol modifications leading to MBP-induced EAE in H2b mice include combination of active and passive immunization, coinjection of IFN-{gamma} (4), and ultra-high doses of encephalitogen or adjuvants. The latter seems to be the case in the present study by Faunce et al., which uses 400 µg of encephalitogen and 4 mg/ml CFA.

Therefore, we do not share Furlan’s surprise about the results reported from Dr. Streilein’s laboratory. Rather, it seems likely that selection of the appropriate Ag and immunization protocol forcing a vigorous Th1 shift can overcome resistance to specific encephalitogens in seemingly insusceptible mouse strains.

References

  1. Faunce, D. E., A. Terajewicz, J. Stein-Streilein. 2004. Cutting edge: in vitro-generated tolerogenic APC induce CD8+ T-regulatory cells that can suppress ongoing experimental autoimmune encephalomyelitis. J. Immunol. 172:1991.[Abstract/Free Full Text]
  2. Furlan, R.. 2004. MBP-specific experimental autoimune encephalomyelitis in C57BL/6 mice. J. Immunol. 173:5.[Free Full Text]
  3. Linker, R. A., E. Rott, H. H. Hofstetter, T. Hanke, K. V. Toyka, and R. Gold. EAE in {beta}-2 microglobulin deficient mice: axonal damage is not dependent on MHC-I restricted immune responses. Submitted for publication.
  4. Shaw, M. K., C. Kim, H. W. Hao, F. Chen, H. Y. Tse. 1996. Induction of myelin basic protein-specific experimental autoimmune encephalomyelitis in C57BL/6 mice: mapping of T cell epitopes and T cell receptor V{beta} gene segment usage. J. Neurosci. Res. 45:690.[Medline]




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