MECHANISMS OF CELLULAR IMMUNE RESPONSES

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Our studies continue to emphasize studies of T cell adhesion and migration, particularly as they relate to interactions with endothelium and related migration into tissue. Our studies have revealed a persuasive, powerful and rapid regulator of cellular F- actin:to depolymerize to levels far below those previously observed and conversely mechanical stimulation causes actin repolymerization in less than 1 second. We hypothesize that mechanosensation is essential to the regulation of cytoskeletal rearrangement, locomotion and cell adhesion, including leukocyte binding to endothelium. We have systematically studied the regulation of chemokine production by endothelial cells and find the rules fit the properties of an amplification system for conveying information from the underlying tissue to passing leukocytes. We have characterized the fibroblastic reticular (FRC) system, which we interpret to be a specialized system for conveying information to the high endothelial cells in lymph node. We find evidence both for soluble mediators within the system and rich display of extracellular matrix determinants which most likely facilitate lymphocyte movement within lymph node. Finally we have investigated protoglycan both on endothelial cells and on T cells. Of particular note in those studies, we find that although chondriotin sulfate is expressed at low level on T cells, that chondroitin sulfate is important for the invasion of T lymphocytes into collagen gels.