Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis

In addition to their well characterized role in allergic inflammation, rece nt data confirm that mast cells play a more extensive role in a variety of immune responses. However, their contribution to autoimmune and neurologic disease processes has not been investigated. Experimental allergic encephal omyelitis (EAE) and its human disease counterpart, multiple sclerosis, are considered to be CD4(+) T cell-mediated autoimmune diseases affecting the c entral nervous system. Several lines of indirect evidence suggest that mast cells could also play a role in the pathogenesis of both the human and mur ine disease. Using a myelin oligodendrocyte glycoprotein (MOG)-induced mode l of acute EAE, we show that mast cell-deficient W/W-V mice exhibit signifi cantly reduced disease incidence, delayed disease onset, and decreased mean clinical scores when compared with their wild-type congenic littermates. N o differences were observed in MOG-specific T and B cell responses between the two groups, indicating that a global T or B cell defect is not present in W/W-V animals. Reconstitution of the: mast cell population in W/W-V mice restores induction of early and severe disease to wild-type levels, sugges ting that mast cells are critical for the full manifestation of disease. Th ese data provide a new mechanism for immune destruction in EAE and indicate that mast calls play a broader role in neurologic inflammation.