Kawasaki Disease (KD) is a childhood disease leading to coronary arteritis. Elevated numbers of CD40L+ platelets in circulation is correlated with risk of heart damage. CD40L is a tumor necrosis family member that binds to CD40 and αIIbβ3, receptors which are also expressed on platelets. A single injection of Lactobacillus casei Cell Wall Extract (LCWE) induces a disease similar to KD in mice, where LCWE superantigen (SAg) reactive T-cells persist in the coronary artery. This phenotype is inconsistent with the fate of SAg-stimulated cells and is likely mediated by co-stimulation. This work shows that stimulation with a SAg induces platelet activation and CD40L expression in vitro. Furthermore, enhanced survival of SAg-reactive T-cells is demonstrated following antibody-mediated CD40L cross-linking. This effect is mediated via inhibition of the extrinsic apoptosis pathway. In addition, CD40 cross-linking is also reported to enhance SAg-reactive T-cell survival by enhancing CD86 expression on APCs and CD28 co-stimulation.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/30165 |
| Date | 01 December 2011 |
| Creators | Arjmand, Parnian |
| Contributors | Yeung, Rae S. M. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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