Demyelination caused by the copper chelator cuprizone halts T cell mediated autoimmune neuroinflammation.

Myelin reactive T cells are central in the development of the autoimmune response leading to CNS destruction in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis (EAE). Investigations on the mechanisms underlying the activation and expansion of myelin reactive T have stressed the importance of non-autoimmune conditions impinging the autoimmune repertoire potentially involved in the disease. Here, we show that CNS injury caused by the toxic cuprizone results in the generation of immunoreactivity towards several myelin components.

The innate immune response to adjuvants dictates the adaptive immune response to autoantigens.

To elucidate the role of innate immunity in susceptibility to the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we induced EAE by immunization with spinal cord homogenate (SCH) plus complete Freund adjuvant or carbonyl iron in 3 inbred rat strains. Lewis are considered "susceptible," PVG/c-Rt7a (PVG) as "semisusceptible," and Brown Norway (BN) as "resistant" to EAE. Immunization with SCH-carbonyl iron resulted in clinical disease in all 3 strains, but the pathologic features of EAE in the resistant BN and the semisusceptible PVG rats differed from those in the Lewis and PVG model of EAE induced with SCH-complete Freund adjuvant.

Nitric oxide contributes to the resistance of young SJL/J mice to experimental autoimmune encephalomyelitis.

EAE development in SJL/J mice is age and sex dependent: young males are EAE resistant; females and adult males are EAE susceptible. By studying splenocytes' IFNgamma and NO production and the induction or the suppression of actively induced EAE by manipulating NO systemic levels, we provide evidence that the failure of young male SJL/J mice to develop EAE lies in the activation of the innate immune system by the immunising stimulus.