CD4+ T-cell subsets in Helicobacter-induced inflammation

The local cytokine milieu is known to influence the differentiation of distinct CD4+ T cell subsets. For example, IL-12 drives the differentiation of IFN-g-secreting Th1 cells, whereas the presence of TGF-beta, IL-6, and IL-23 leads to the differentiation and expansion of IL-17-producing Th17 cells. IL-23 has recently been shown to play an important role in the development of chronic inflammatory diseases such as inflammatory bowel disease. This inflammatory disorder of the intestinal tract is caused in part by an inappropriate immune response to the bacterial flora. Using a model of bacterial-induced colitis, this project will focus on CD4+ T cell responses to Helicobacter hepaticus. Recent data from the lab have shown that infection with H. hepaticus leads to the expansion of both Th1 and Th17 cells as well as other populations of cytokine-secreting CD4+ T lymphocytes. This project will investigate how these different CD4+ T cell subsets develop and their role in inflammation. The project will involve extensive training in cellular and molecular immunology.