Abstract
Stimulatory and inhibitory co-receptors play fundamental roles in the regulation of the immune system. We describe a new mouse model of spontaneous autoimmune disease. Activation-induced cytidine deaminase-linked autoimmunity (aida) mice harbor a loss-of-function mutation in the gene encoding lymphocyte activation gene 3 (LAG-3), an inhibitory co-receptor. Although LAG-3 deficiency alone did not induce autoimmunity in nonautoimmune-prone mouse strains, it induced lethal myocarditis in BALB/c mice deficient for the gene encoding the inhibitory co-receptor programmed cell death 1 (PD-1). In addition, LAG-3 deficiency alone accelerated type 1 diabetes mellitus in nonobese diabetic mice. These results demonstrate that LAG-3 acts synergistically with PD-1 and/or other immunoregulatory genes to prevent autoimmunity in mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Antigens, Surface / genetics
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Antigens, Surface / metabolism*
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Apoptosis Regulatory Proteins / deficiency
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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Autoimmunity / genetics
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Autoimmunity / immunology*
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DNA Primers / genetics
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Diabetes Mellitus, Type 1 / genetics
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Disease Models, Animal*
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Flow Cytometry
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Lymphocyte Activation / immunology*
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Lymphocyte Activation Gene 3 Protein
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Microsatellite Repeats / genetics
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Myocarditis / genetics
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Polymorphism, Restriction Fragment Length
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Polymorphism, Single Nucleotide
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Programmed Cell Death 1 Receptor
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes, Regulatory / immunology
Substances
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Antigens, CD
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Antigens, Surface
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Apoptosis Regulatory Proteins
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DNA Primers
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Pdcd1 protein, mouse
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Programmed Cell Death 1 Receptor
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Lymphocyte Activation Gene 3 Protein
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Lag3 protein, mouse