The general goal of this proposal is to study the interaction of T cells with cell types of the cardiac microenvironment with regard to defining the types of interactions that occur and defining the effects of T cell-cardiac microenvironment interactions on both T cells and on non-lymphoid cells (myocytes, fibroblasts, dendritic cells) within cardiac allografts.
The specific aims of the proposal are 1) to establish fibroblast and dendritic cell cultures from cardiac tissue and to prepare fresh suspensions of cardiac myocytes in order to determine the ability of all three cell types to bind to T cells at various stages of T cell maturation and activation; 2) to study the sequelae of fibroblast-T cell interactions, dendritic cell-T cell interactions and myocyte-T cell interactions on T cells. Specifically, the interactions of LFA-3+ fibroblasts, LFA-3+ dendritic cells and LFA-3+ myocytes with CD2+ T cells will be studied and the effect of such interactions on T cell activation and function determined. 3) Finally, we will study the sequelae of T cell interactions with cardiac microenvironment stromal components with regard to regulation of stromal cell surface antigen expression, and cytokine production by cardiac fibroblasts, dendritic cells, and myocytes. Thus, this proposal will study mechanisms of T cell activation during human cardiac allograft rejection. It is hoped that these studies will help define mechanisms of T cell activation within the heart with the long term goal of being able to specifically interrupt these mechanisms of T cell activation, thus preventing cardiac allograft rejection.
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