Abstract
Clinical and immunological similarities between Kawasaki Disease (KD) and classical superantigen (SAg) mediated diseases such as the toxic shock syndrome lend credence to the hypothesis that SAgs may be involved in the aetio-pathogenesis of the disease. There are only limited data available, however, examining how SAgs may cause vasculitis. We have, therefore, examined a possible mechanism of superantigenic-induced T cell/endothelial cell activation. To confirm the ability of SAgs to stimulate T lymphocytes, peripheral blood mononuclear cells (PBMCs) were incubated for 4 hours with 10ng/ml of TSST-1 or 100 ng/ml of SEB. This resulted in a Vb specific activation of T lymphocytes (Vb2 for TSST-1, Vb3 and 12 for SEB) as determined by expression of the early activation marker CD69 measured by flow cytometric analysis. Human umbilical vein endothelial cells (HUVECs), with or without pre-treatment with gamma interferon (g-INF) to induce MHC class II expression, and subsequently incubated for 4 or 24 hours with 100 ng/ml of the SAg SEB did not result in upregulation of the endothelial cell adhesion molecules ICAM-1, VCAM, E-selectin, or P-selectin. However, the addition of TSST-1 or SEB to a co-culture of purified CD3+ T lymphocytes (containing less than 0.8% HLA class II positive cells) and HUVECs resulted in up-regulation at 4 hours of ICAM-1, VCAM, and E-selectin (for TSST-1), and E-selectin (for SEB) on HUVECs pretreated with g-INF for 48 hours. At 24 hours, upregulation of ICAM-1, VCAM, and E-selectin occurred with both TSST-1 and SEB irrespective of HUVEC pre-treatment with g-INF. Conclusion: Our data underscore the ability of SAgs to cause T cell activation and, moreover, suggest a role for the HLA class II + endothelial cell as a superantigen presenting cell. The resultant T cell activation and subsequent upregulation of endothelial cell adhesion molecules could be one mechanism whereby SAgs cause vasculitis.
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Brogan, P., Shah, V., Klein, N. et al. Superantigenic Activation of T Lymphocytes and Endothelial Cells: A Mechanism for Superantigen-induced Vasculitis. Pediatr Res 53, 168 (2003). https://doi.org/10.1203/00006450-200301000-00086
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DOI: https://doi.org/10.1203/00006450-200301000-00086