Lymphocyte recirculation results in the continuous supply of T and B cells to lymph nodes (LN), intestinal lymphoid tissues (ILT) and spleen and provides a system for redistribution of lymphocytes within these tissues. The first step in entry of blood lymphocytes into LN and ILT is the binding of these cells to venules lined by high endothelium (HEV). The long term goal of our research is to elucidate in humans the molecular mechanisms of lymphocyte adhesion to the high endothelium and to delineate the relationship of abnormalities in lymphocyte-HEV interactions to disease processes. The primary objectives of this proposal are to identify human high endothelial binding lymphocytes and to analyze surface molecules of human cells which mediate adhesion. This function of human lymphocytes will be assessed through the use of in vitro HEV adherence assays utilyzing both rat and human HEV. We will identify the class and subclass of lymphocytes which bind to these vessels; specific adhesion molecules will be sought using a rabbit antibody with cross-specie reactivity. We will test the hypothesis that different lymphocyte populations and cell surface structures bind to HEV of LN and HEV of ILT. We plan to produce mouse monoclonal antibodies to high endothelial adhesion molecules of human lymphocytes and will attempt to devise methods for the isolation of viable high endothelial cells. The in vitro HEV adherence assay wil be employed to examine the properties of blood lymphocytes of patients with lymphomas, leukemia and in immunosuppressed states.
