Role of antibody and complement in determining site of lesion development in an animal model of multiple sclerosis

Greer, Judith and Muller, Diane (2010). Role of antibody and complement in determining site of lesion development in an animal model of multiple sclerosis. In: ISNI 2010 Abstracts: Tuesday October 26th, 2010 10th Course of the European School of Neuroimmunology. 2010 10th Course of the European School of Neuroimmunology, Sitges, Spain, (161-162). 26-30 October 2010.

Author Greer, Judith
Muller, Diane
Title of paper Role of antibody and complement in determining site of lesion development in an animal model of multiple sclerosis
Conference name 2010 10th Course of the European School of Neuroimmunology
Conference location Sitges, Spain
Conference dates 26-30 October 2010
Proceedings title ISNI 2010 Abstracts: Tuesday October 26th, 2010 10th Course of the European School of Neuroimmunology   Check publisher's open access policy
Journal name Journal of Neuroimmunology   Check publisher's open access policy
Place of Publication Amsterdam, Netherlands
Publisher Elsevier
Publication Year 2010
Sub-type Published abstract
ISSN 0165-5728
1872-8421
Volume 228
Issue 1-2
Start page 161
End page 162
Total pages 2
Language eng
Abstract/Summary We have previously described an atypical form of experimental autoimmune encephalomyelitis (EAE), which can be actively induced in C3H/HeJ mice by injection of myelin proteolipid protein (PLP) peptide PLP190–209 in adjuvant, and which results in development of lesions that are restricted predominantly to the brainstem and cerebellum of the mice. Subsequently, we have used PLP190–209-specific T cells to passively induce EAE. To our surprise, these mice consistently developed lesions in the brainstem, but never developed lesions in the cerebellum. Since the mice with actively induced EAE produce both PLP190–209-specific T cells and antibodies, we have investigated the role of antibody in the development of cerebellar lesions in this model. EAEwas induced by passive transfer of PLP190–209-specificTcells ± immunoaffinity-purified PLP190–209- specific antibody or an irrelevant antibody as control. Within 2 days of onset of neurological signs, mice were perfused. One micron sections were cut every 10 μm through the brainstem and cerebellum and stained with cresyl violet to assess lesions. Whole cross-sections were photographed and the percentage area of each cerebellum covered by lesions was determined using NIH Image software. To assess the role of complement, EAE was actively induced, and then mice were treated daily with injections of cobra venom factor (CVF),which inhibits complement. These mice developed EAE and were assessed as above. CVF has a short half-life in serum, and therefore, in some mice, CVF treatment was stopped at EAE onset, and 4 days later mice were assessed for lesions in the cerebellum. Mice with passively transferred EAE induced by T cells alone (n=30) all developed EAE with lesions in the brainstem, but not the cerebellum. In contrast, 60% of mice receiving T cells + PLP190–209-specific antibody developed lesions in the cerebellum. Actively immunized mice receiving CVF developed no lesions in the cerebellum; however, 4 days after stopping CVF treatment, lesions could once more be observed in the cerebellum. These findings strongly suggest that PLP-specific antibody plays a role in determining the location of lesions in this animal model of MS, and that the antibody effects are complement-mediated. We suggest that retargeting of lesion distribution by antibody could be a potentially clinically important and previously unappreciated element of antibody action in MS and, as such, require further investigation.
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Document type: Conference Paper
Collection: UQ Centre for Clinical Research Publications
 
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Created: Sun, 23 Jan 2011, 00:03:22 EST