(B) Histological analysis of cerebellum and spinal cord from a sick TCR 1640 mouse (RR mouse) with ataxia and classical paralysis. Disease kinetic of genders in TCR 1640 mice was not statistically significant (P = 0.304) but differed significantly between sexes of TCR 1640 × IgH MOG mice (P = 0.0004). TCR 1640 females (f), n = 12 males (m), n = × IgH MOG females, n = 20 males, n = × Mog −/− mice, n = 6.

Shown is the spontaneous incidence of first signs of ataxia or classical EAE-like symptoms in TCR 1640 (left) and double-transgenic TCR 1640 × IgH MOG (right) mice. (A) Male and female single-transgenic TCR 1640 compared with double-transgenic TCR 1640 × IgH MOG mice. Spontaneous RR-EAE in TCR transgenic SJL/J mice. RR mice constitute the first spontaneous animal model for the most common form of multiple sclerosis (MS), RR MS. The secreted autoantibodies are pathogenic, enhancing demyelinating EAE episodes. The expanded autoreactive B cells produce autoantibodies binding to a conformational epitope on the native MOG protein while ignoring the T cell target peptide.

Transgenic T cells seem to expand MOG autoreactive B cells from the endogenous repertoire. There is no spontaneous EAE development in B cell-depleted mice or in transgenic mice lacking MOG. Development of spontaneous EAE depends on the presence of an intact B cell compartment and on the expression of MOG autoantigen. Backcrossed to the SJL/J background, most RR mice spontaneously develop RR experimental autoimmune encephalomyelitis (EAE) with episodes often altering between different central nervous system tissues like the cerebellum, optic nerve, and spinal cord. We describe new T cell receptor (TCR) transgenic mice (relapsing-remitting mice) carrying a TCR specific for myelin oligodendrocyte glycoprotein (MOG) peptide 92-106 in the context of I-A(s).

Mog autoimmune