MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are mediated by lymphocytes reactive to brain antigens. Two possibilities regarding the initiation of inflammation in MS have been considered. The first is that autoreactive CD4 T cells, as shown in EAE, enter the normal brain parenchyma and initiate an autoimmune response against brain Ags. The second possibility is that virus Ag-specific T cells cross into the brain and target virally infected CNS-resident APC, as shown in virus-induced encephalitis. From both these possibilities, it clearly emerges that the emigration of autoreactive lymphocytes through the blood-brain barrier (BBB) represents a critical pathogenetic event in the initiation of CNS inflammation.
Although neutrophils are typically absent from brain taken at autopsy in the most common forms of MS, where mononuclear cell infiltration is predominant, higher numbers of circulating neutrophils with a primed phenotype were found in MS patients in comparison to healthy subjects.
During EAE the elimination of neutrophils or the inhibition of their recruitment show some protective effects, suggesting a detrimental role in disease pathogenesis. However, the phenotype and functions of neutrophil in MS is still largely unknown, and their interaction with other immune and neuronal cells taking part in disease pathogenesis are almost completely unexplored.
