Abstract
Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis is currently the best animal model for Kawasaki disease. Kawasaki disease is a multisystem vasculitis and the leading cause of acquired heart disease in children of the developed world. In this study, we show that responses to LCWE possess all the hallmarks of a superantigen (SAg)-mediated response. LCWE induces massive activation of naive T lymphocytes, as measured by both in vitro proliferation and production of tumor necrosis factor-alpha. Interestingly, LCWE-mediated responses require antigen presentation but not processing by accessory cells. As in the case of other known SAgs, the response to LCWE is MHC non-classically restricted, and there exists a hierarchy of differing class II MHC in the ability to present LCWE. The most compelling evidence of superantigenic activity of LCWE is its ability to induce the characteristic activation and proliferation of T cells expressing specific T cell receptor variable beta families 2, 4, 6 and 14, followed by the deletion of these reactive cells. Most importantly, superantigenic activity of LCWE correlates with its ability to induce coronary vasculitis upon injection into mice. Only LCWE preparations possessing superantigenic properties mediate cellular infiltrations in the cardiac tissue leading to coronary arteritis in vivo.Taken together, these findings demonstrate that LCWE contains a novel superantigen, the activity of which may lead to disease pathogenesis. Since LCWE-mediated coronary arteritis in mice is currently the best animal model of Kawasaki disease, understanding of the mechanisms leading from immune activation to coronary artery lesions in this model will be of great benefit in designing new treatment strategies, reducing vascular damage, and, more importantly, the significant morbidity and mortality associated with Kawasaki disease.
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Duong, T., Silverman, E., Bissessar, M. et al. A Superantigen in Lactobacillus casei Cell Wall Extract Induces Coronary Arteritis: An Animal Model for Kawasaki Diseasee. Pediatr Res 53, 174 (2003). https://doi.org/10.1203/00006450-200301000-00124
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DOI: https://doi.org/10.1203/00006450-200301000-00124