Abstracts (complete list) - Wissenschaft Online

Bernadette Pöllinger, Gurumoorthy Krishnamoorthy, Michael Bösl, Hans Lassmann,
Andeas Holz, Hartmut Wekerle, Florian C. Kurschus*
RR Mouse: Spontaneous relapsing remitting EAE in SJL/J mice
expressing a MOG responsive T cell receptor
Myelin oligodendrocyte glycoprotein (MOG) is regarded as major autoantigen in Multiple
Sclerosis (MS) and its animal model • experimental autoimmune encephalomyelitis
(EAE). Its anatomic localization on the outermost layer on central nervous system
(CNS) myelin sheets suites it perfectly as target for auto-antibodies. We recently
described a double transgenic C57BL/6 (H-2b ) mouse strain carrying a MOG specific T
cell receptor along with a MOG specific immunoglobulin H chain (Krishnamoorthy G. et
al., J Clin Invest. 2006;116:2385-2392). These mice develop spontaneous autoimmune
disease affecting spinal cord and optic nerve, but sparing brain and cerebellum, thus
resembling human opticospinal myelitis (Devic disease).
In order to explore the possible effect of genetic factors on disease expression, we now
report about new similar transgenic mouse lines, but on SJL/J (H-2s ) background. We
created three T cell receptor (TCR) transgenic lines bearing CD4 cells specific for MOG92- 106 presented by I-AS . These lines differ in their penetrance of transgene expression on
CD4 cells (TCR1640 , 70%; TCR1639 , 20%; TCR1586 , 5%). In contrast to the Devic model,
single (TCR-) transgenic SJL/J mice spontaneously develop EAE at high frequency.
Disease occurs in more than 75 % of TCR1640 but only in about 15 % of TCR1586 mice,
if bred on SJL/J, but not on the B10.S background. Spontaneous EAE in many cases
takes a relapsing-remitting course, with individual disease bouts affecting distinct CNS
parts (cerebellum vs. spinal cord). Intriguingly TCR1640 and diseased TCR1586 SJL/J
mice select and activate endogenous MOG-specific B cells to produce MOG reactive IgG1
and IgG2ab autoantibodies. This new form of autoimmune B cell recruitment does not
occur on the MOG knockout -or B10.S background and may therefore involve MOG
exposure to the immune system during preclinical EAE lesions.
The RR mouse is the animal model most faithfully recapitulating the most frequently
occurring human MS variant. It will be of use studying issues including relapse
generation, autoimmune T-B cell cooperation, and drug discovery.