The long term goals of this project are to gain further insight into the mechanisms that govern the development, activation and function of CD4+ T cells with restricted cytokine profiles in antigen specific responses. The objectives of this project are to: 1. Determine the precise mechanisms by which cytokine profiles develop in keyhole limpet hemocyanin (KLH)-specific memory T cells, and how the type of antigen presenting cell (APC) and its activation state, antigen concentration, and APC costimulator molecules influence this development. 2. Analyze how cytokine synthesis is differentially regulated in different strains of mice. 3. Compare the role of B cells in directing the development of lymphokine profiles in primed versus unprimed CD4+ T cells. To accomplish these aims we have established several antigen specific models to follow the development of restricted lymphokine profiles. We have generated a substantial amount of preliminary data demonstrating that IL-4 synthesis in KLH primed CD4+ T cells is greatly affected by the concentrations of KLH in vitro, and is preferentially enhanced by antigen presentation by primed B cells. In addition, we have several lines of evidence that indicate that regulation of lymphokine synthesis is distinct in different strains of mice, due to differences at the level of the antigen presentation cell. Finally, we have established accurate and sensitive assays for the cytokines IL-2, IL-3 and IL-4, IL-5, IL-6, IL-10, IFN-gamma. In as much as responses to different types of pathogens-require distinct functions of T cells, the development of T cell subsets with restricted cytokine profiles is of fundamental importance in regulation of the immune response. Knowledge of the precise mechanisms that regulate the development of CD4+ T cells subsets is critical in understanding and treating diseases such as allergy, autoimmune disease, susceptibility to infection, or cancer, and in vaccine development, in which the development of CD4+ T cells with inappropriate cytokine profiles may be detrimental to the host.
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