DIFFERENTIAL ACTIVATION REQUIREMENTS OF CLONED T CELLS

该项目的长期目标是进一步深入了解

The long term goal of this project is to gain further insight into the mechanisms governing the activation of CD4+ T cell subsets, and the mechanisms governing T-B cell interactions which result in the induction of antibody synthesis.' The specific aims of this project are to: 1. precisely define the conditions which lead to the activation and expansion of Th1 versus Th2 T cells. 2. examine the characteristics of Th1 and Th2 clones which are capable of inducing antibody synthesis, and dissect the mechanism by which they perform this function. 3. examine the role of Th1 and Th2 "nonhelper" clones in the induction of antibody synthesis. To perform this project, our lab has generated a large panel of nominal antigen specific Th1 and Th2 clones, which are heterogeneous with regard to their profile of lymphokine production and with regard to their ability to provide cognate help in the induction of antibody synthesis. In addition, we have established accurate and sensitive ELISA assays for IgG, IgG subclasses, IgA, and IgE, and have enlisted the support of other investigators to help us apply molecular biology techniques in the analysis of our clones. With our ability to purify B cell and accessory cell populations, we have available powerful tools to analyze T cell activation and function at the clonal level. Since isotype specific responses require the presence of distinct lymphokines, and since responses to different types of pathogens require distinct functions of T cells, the division of CD4+ T cells into subsets may be of fundamental importance in the regulation of immune responses. Thus understanding of the requirements for selective activation of one type of CD4+ T cell subset over another, and of the role of each subset in the induction of antibody synthesis is crucial for future development of strategies to favorably manipulate the immune system in multiple disease states.