Control of the autoimmune response by type 2 nitric oxide synthase

Immune defense against pathogens often requires NO, synthesized by type 2 N O synthase (NOS2). To discern whether this axis could participate in an aut oimmune response, we immunized NOS2-deficient mice with the autoantigen ace tylcholine receptor, inducing muscle weakness characteristic of myasthenia gravis, a T cell-dependent Ab-mediated autoimmune disease. We found that th e acetylcholine receptor-immunized NOS2-deficient mice developed an exacerb ated form of myasthenia gravis, and demonstrated that NOS2 expression limit s autoreactive T cell determinant spreading and diversification of the auto antibody repertoire, a process driven by macrophages. Thus, NOS2/NO is impo rtant for silencing autoreactive T cells and may restrict bystander autoimm une reactions following the innate immune response.