Aktuelle Neurologie 2005; 32 - V190
DOI: 10.1055/s-2005-919257

Development of an EAE model for histopathological subtype II of MS: role of humeral immune system

T Ziemssen 1, H Schneider 1, J Bauer 1, A Iglesias 1
  • 1Dresden; Vienna, A; Basel, CH

Introduction: The considerable heterogeneity in the pathogenesis of MS is evidenced by identification of 4 distinct subtypes of MS. In subtype II lesions, humeral immune components (typical deposition of immunoglobulins and complement) are involved in addition to T cell and macrophage infiltration. Patients with subtype II lesions seem to respond to specific treatment regimes like plasma exchange. In addition, Berger et al. (2003) have shown that anti-myelin antibodies (Ab) (especially those directed to myelin oligodendrocytic glycoprotein (MOG)) could serve as marker in MS.

Design/Methods: To investigate the role of the humeral anti-myelin immune system, transgenic TH mice expressing a targeted heavy chain of the demyelinating anti-MOG 8.18c5 antibody were used for active and passive immunization experiments to induce EAE. Purified resting or activated B cells as well as anti-MOG antibodies were used for transfer experiments in wild-type (WT) animals. Clinical disease, histopathology and immunological parameters were investigated.

Results: TH mice always developed significantly earlier and much more severe clinical disease of active and passive EAE compared to WT mice. Myelin-specific T cell lines which were non-encephalitogenic in WT mice or active immunization protocols tested not to be able to induce EAE in WT mice lead to development of EAE in TH mice. But there was no unspecific EAE induction in TH mice by treatment with pertussis toxin or adjuvant CFA. Histopathologically, there was no increase in the number of B cells in EAE infiltrates of TH mice, but large deposits of anti-MOG Ab and complement. The large inflammatory infiltrates observed in these animals include significantly increased numbers of cells of the myeloid lineage like macrophages and activated microglia which correlated quite well with increased demyelination, axonal loss and clinical disease.

Conclusions: We developed an EAE model of histopathological subtype II of MS using TH mice with characteristic histopathology and severe and acute clinical disease. This model can serve as an excellent tool to evaluate function of the blood-brain barrier (BBB). Anti-myelin B cells and Abs are not pathogenic alone, but can accelerate and exacerbate an even subclinical EAE, possibly by enhanced antigen presentation or effector cell recruitment.