免疫学

Experimental autoimmune encephalomyelitis (EAE) is a widely used rodent model of multiple sclerosis (MS), typically induced with pertussis toxin (PTX) to achieve robust disease onset. However, PTX has been shown to exert broad immunomodulatory effects that include disruption of G protein-coupled receptor (GPCR) signaling, altered T-cell response, and exogenous suppression of regulatory T cells, all of which are not present in human MS pathophysiology. Moreover, PTX also obscures the sex differences observed in MS, limiting the translational value of EAE models that rely on it. Given EAE’s widespread use in preclinical therapeutic testing, there is a critical need for a model that better recapitulates both clinical and immunological features of MS without PTX-induced confounds. Here, we demonstrate a non-pertussis toxin (non-PTX) EAE model in C57BL/6 mice, using optimized concentrations of complete Freund’s adjuvant (CFA), Mycobacterium tuberculosis, and myelin oligodendrocyte glycoprotein (MOG_35-55) peptide. This model recapitulates hallmark features of MS that include demyelination, neuroinflammation, motor deficits, and neuropathic pain. Importantly, it retains sex-specific differences in disease onset and pathology, providing a more physiologically and clinically relevant platform for mechanistic and translational MS research.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system (CNS). It is characterized by focal demyelination and inflammatory responses mediated by myelin-specific autoreactive CD4⁺ T cells. Using a passive transfer model of EAE in mice, we have demonstrated that regional specific neural signals by sensory-sympathetic communications create gateways for immune cells at specific blood vessels of the CNS, a phenomenon known as the gateway reflex (Arima et al., 2012; Tracey, 2012; Arima et al., 2013; Sabharwal et al., 2014; Arima et al., 2015b). Here we describe protocols for passive transfer model of EAE using freshly isolated (MOG)-specific CD4⁺ T cells or periodically restimulated MOG-specific CD4⁺ T cell lines, which are suitable for tracking pathogenic CD4⁺ T cells in vivo, particularly in the CNS (Ogura et al., 2008; Arima et al., 2012 and 2015b).