Emeritus Group Neuroimmunology

Transgenic models of spontaneous EAE

Scientific innovation is the product of fresh ideas and innovative technology. With this in mind, we have paid particular attention to the in-house development of new transgenic models of MS, and on new approaches to functional image the unfolding autoimmune response.

In most experimental studies, Experimental Autoimmune Encephalomyelitis (EAE) is induced in rodents either by active immunization against myelin autoantigen suspended in overwhelmingly strong immune adjuvants, or by injection of a large number of pre-activated myelin specific T lymphocytes. These models represent isolated immunological and histopathological aspects of the human disease. However, none of these models simulate the full clinical and pathological complexity of human MS. In particular, with their artificial mode of induction, these models are not suitable to study the triggers of CNS autoimmunity.

To overcome these limitations, we have established two spontaneous EAE models – one in the C57BL/6 background (OSE mouse) and another in the SJL/J background (RR mouse).

OSE (opticospinal encephalomyelitis) mice are double-transgenic animals, carrying transgenic T cells specific for myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) and transgenic B cells binding native MOG antigen (1).  About 50% of the mice develop spontaneously OSE with lesions restricted to the spinal cord and the optic nerve, but mostly sparing the brain. OSE typically takes a chronic progressive course without marked remission or relapses (2).

RR (relapsing-remitting) mice are single-transgenic animals, which express T cells using a receptor specific for the MOG peptide 92-106 in the context of MHC class II (I-As) (3). More than 90% of RR mice spontaneously develop a relapsing-remitting course of EAE within one year. Lesions are distributed throughout the CNS including spinal cord, optic nerve, brain stem and cerebellum.

These transgenic models provide an unique opportunity to study microbial triggers of brain autoimmune T cell clones, recruitment of autoimmune B cells from the native repertoire as well as cell-to-cell interactions and migration events following initial activation.

1. T. Litzenburger et al., J. Exp. Med. 188, 169 (1998). 

2. G. Krishnamoorthy, H. Lassmann, H. Wekerle, A. Holz, J. Clin. Invest. 116, 2385 (2006).     

3. B. Pöllinger et al., J. Exp. Med. 206, 1303 (2009).

 
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