The broad objective of this project is to define how vascular endothelial cells and lymphocytes functionally interact with one another in ways which modify immune and inflammatory-responses to foreign antigens. This proposal is based on a substantial body of -data from predominantly in vitro experiments indicating that endothelium and T lymphocytes can specifically interact with one another and alter each other's phenotype. The newly proposed experiments encompass two fundamental advancements from these preceding studies. First, new in vitro experiments will thoroughly analyze the specificity and consequences of lymphocyte:endothelial interactions using sophisticated immunologic models of T cell function. Second, the in vivo significance of the in vitro phenomena will be tested using newly developed, and potentially powerful animal models. The proposed experiments are directed at defining the role of endothelium in regulating lymphocyte activation and immune responses at sites of antigen challenge. This will require examination of lymphocyte adhesion events, T cell activation responses such as cytokine secretion, and subsequent inflammatory responses involving other leukocytes.
Specific Aim 1 : TO CHARACTERIZE ANTIGEN-SPECIFIC INTERACTIONS BETWEEN ENDOTHELIUM AND T LYMPHOCYTES.
Specific Aim 2 : TO DEFINE SPECIFIC T CELL RECRUITMENT FUNCTIONS OF ENDOTHELIUM IN VITRO.
Specific Aim 3 : TO ASSESS THE ROLES OF VASCULAR ENDOTHELIUM IN T CELL ACTIVATION AND RECRUITMENT IN VIVO.
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