Costimulation-mediated Rescue of Superantigen-activated T cells in an Animal Model of Kawasaki Disease

Lactobacillus casei cell wall extract (LCWE)- induced coronary arteritis in mice models Kawasaki disease (KD). LCWE injections consist of T-cell dependent factors that expand superantigen (SAg)-activated T-cell receptor (TCR) Vβ6+ cells, and T-cell independent factors (i.e. TLR2 activity) that localize and sustain the immune response. TLR2 can upregulate costimulatory molecules to rescue SAg-activated T-cells from apoptosis. Accordingly, SAg-activated costimulation-rescued TCRVβ6+ cells are predicted to express activation markers, produce cytokines and be able to induce coronary arteritis. MAM was identified as a SAg able to activate TCRVβ6+ cells in a manner similar to LCWE; however a combination of MAM and TLR2 agonist Pam3Cys could not induce coronary arteritis. As another marker of disease, leukocyte recruitment molecule expression in the hearts of MAM+Pam3Cys- injected mice was found to be lower than in LCWE- injected mice. Therefore, LCWE contains unique features beyond TCRVβ6 stimulation and TLR2 activity that are important for disease induction.