Meningeal mast cells facilitate effector T cell function in a murine model of multiple sclerosis. (P4095)

Abstract

Abstract Experimental autoimmune encephalitomyelitis (EAE) is a rodent model of the CNS demyelinating disease, multiple sclerosis. In EAE, autoreactive T cells are the major orchestrators of myelin damage. Recent data suggests that after priming in secondary lymphoid organs, these T cells are reactivated prior to entry into the CNS. This reactivation is thought to enhance effector function, however the details describing this mechanism are lacking. The meninges, tissues surrounding the CNS, have recently been appreciated as sites of immune responses in early EAE. Mast cells (MCs) residing in the meninges are activated within a day of disease induction and release neutrophil recruitment factors essential for the generation of severe disease. T cells also traffic to the meninges in early EAE suggesting the potential for T cell-MC interactions. Within 24 hours of adoptive transfer, MOG-specific effector CD4+ T cells accumulate in the meninges, an event dependent on the presence of MCs, and acquire the ability to produce the encephalitogenic cytokine, GM-CSF. T cell transfer also results in meningeal MC production of IL-1β. In vitro, co-culture of effector T cells with either wild type or IL-1β-/- MCs confirm that T cells can directly stimulate IL-1β production by MCs, which in turn elicits T cell expression of GM-CSF. These data support the concept that T cell-MC interactions in the meninges facilitate the acquisition of pathogenic effector functions necessary for severe disease.