Superantigens are bacterial and viral proteins that can mediate non-specific activation of T cells by crosslinking of T cell receptor V beta region sequences with the MHC class II molecules on accessory cells. The staphylococcal enterotoxins A and B (SEA, SEB) have been identified in cultures from the skin of patients with chronic atopic dermatitis (AD) and are thought to promote T cell proliferation in AD. The T cells in AD are predominantly of the Th2 phenotype. Mast cells have been implicated as a source of IL-4 that can drive this Th2 response, since degranulation of mast cells is a prominent feature of atopic inflammation. However, the mechanism by which superantigens stimulate mast cells to release IL-4 and other mediators is unclear. This project is based on the hypothesis that mast cells are stimulated during interactions with superantigen and T cells and subsequently release IL-4 and other mediators found in atopic inflammation. The applicant will study the ability of mast cells to present superantigen via their MHC class II molecules as well as the ability of mast cells to drive a Th2 response. Specifically, the applicant will determine the cytokine profiles of T cells and mast cells following in vitro stimulation of peripheral T cells with a mast cell line presenting superantigens. She will investigate (1) whether modulation of mast cell function by cytokines influences the ability of mast cells to present superantigen and (2) whether superantigen activation of mast cells occurs through MHC class II molecule crosslinking. Finally, she will determine whether AD T cells respond differently than normal T cells to superantigen stimulation.
| Mordes, John P; Cort, Laura; Norowski, Elaine et al. (2009) Analysis of the rat Iddm14 diabetes susceptibility locus in multiple rat strains: identification of a susceptibility haplotype in the Tcrb-V locus. Mamm Genome 20:162-9 |
