Antigen-indipendent peripheral immune. Activation precedes clinical and mri evidence of disease activity in MS

Central nervous system (CNS) lesions typical of multiple sclerosis (MS) are characterized by demyelinating inflammatory infiltrates that contain few CNS antigen-specific autoreactive T cells and a multitude of pathogenic non-specific lymphocytes. We report that in patients with MS the combined action of interferon-y, tumor necrosis factor CC , interleukin (IL)-2 and IL-6 leads to the activation of the majority of peripheral T cells (mainly CD4memory) by promoting a persistent intracellular calcium increase via two indipendent signaling pathways. The activation of these pathways, which is indipendent from myelin antigens, precedes by two weeks phase? of diseip a