Superantigens (SAgs) are implicated in the initiation of many diseases, including Kawasaki disease (KD), a multi-system vasculitis that leads to persistent inflammation and damage of coronary arteries. T cells are central to the pathogenesis of SAg-mediated diseases. Lactobacillus casei cell wall extract (LCWE) induces a disease in mice that resembles human KD, and contains a novel SAg. Despite the fact that SAg-activated T cells undergo apoptosis, they persist and are necessary for coronary inflammation in this model of KD. We report rescue from apoptosis of SAg-stimulated T cells in vitro by costimulation through CD28 or 4-1BB. CD28- or 4-1BB-mediated signaling stimulated concurrently with SAg upregulated the anti-apoptotic factor Bcl-XL. In vivo, co-injection of LCWE and a 4-1BB agonist aggravated coronary disease. These findings suggest that costimulation of T cells affects extent of illness in this model of KD, and supports targeting costimulation as a therapeutic intervention in SAg-triggered diseases.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/18898 |
| Date | 15 February 2010 |
| Creators | Moolani, Yasmin |
| Contributors | Yeung, Rae S. M. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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