Kawasaki disease (KD) is a multisystem vasculitis with predilection for the coronary arteries. Although the cause of KD remains elusive, there is evidence to suggest a superantigenic trigger. When T-cells are activated by a superantigen (SAg) they undergo massive proliferation but eventually apoptose; however, in KD, we hypothesize that these T-cells persist and infiltrate the coronary arteries. Previous studies have shown that enhanced costimulation through CD28 or 4-1BB rescues T-cells from apoptosis and exacerbates disease in a mouse model of KD. Our results suggest that this signal needs to be initiated close in timing to that of the SAg. In addition, the two molecules can act independently of one another, but are not additive. Also, stimulation of the 4-1BB pathway in the presence of a SAg elicits a Th1 phenotype. Lastly, TRAF1 regulates this enhanced survival downstream of 4-1BB. Thus, these results provide new insights into the effects of costimulation in SAg-mediated disease, and suggest that these pathways need to be targeted early to abrogate the enhanced survival of SAg-activated T-cells.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/30156 |
| Date | 01 December 2011 |
| Creators | Almeida, Fiona M. |
| Contributors | Yeung, Rae S. M. |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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