PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice

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.

DOI: 10.1084/jem.20100466

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@inproceedings{Okazaki2011PD1AL, title={PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice}, author={Taku Okazaki and Il-mi Okazaki and Jian Xiong Wang and Daisuke Sugiura and Fumio Nakaki and Taku Yoshida and Yu Kato and Sidonia Fagarasan and Masamichi Muramatsu and Tomoo Eto and Kyoji Hioki and Tasuku Honjo}, booktitle={The Journal of experimental medicine}, year={2011} }