Control of the autoimmune response by type 2 nitric oxide synthase.
Immune defense against pathogens often requires NO, synthesized by type 2 NO synthase (NOS2). To discern whether this axis could participate in an autoimmune response, we immunized NOS2-deficient mice with the autoantigen acetylcholine receptor, inducing muscle weakness characteristic of myasthenia gravis, a T cell-dependent Ab-mediated autoimmune disease. We found that the acetylcholine receptor-immunized NOS2-deficient mice developed an exacerbated form of myasthenia gravis, and demonstrated that NOS2 expression limits autoreactive T cell determinant spreading and diversification of the autoantibody repertoire, a process driven by macrophages. Thus, NOS2/NO is important for silencing autoreactive T cells and may restrict bystander autoimmune reactions following the innate immune response.
Shi
F D
FD
Department of Immunology, IMM-23, The Scripps Research Institute, La Jolla, CA 92037, USA.
Flodström
M
M
Kim
S H
SH
Pakala
S
S
Cleary
M
M
Ljunggren
H G
HG
Sarvetnick
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000008:administration & dosage; D015551:Autoimmunity / Q000502:physiology*; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse