Faculty

morris-dailey@uiowa.edu Voice: 319-335-8184

MORRIS 0. DAILEY, M.D., Ph.D. Associate Professor Flow Cytometry Pathology - 145B Medical Research Center Iowa City, IA 52242-1182 Ph.D. University of Chicago, 1976 M.D. University of Chicago, 1977 Pathology Residency, Stanford University, 1977-79 Pathology Fellowship, Stanford University, 1979-83

The projects in my laboratory examine a number of cell surface receptor proteins that mediate intercellular recognition in the immune system. The specific recognition of different cell types is important in cell-to-cell interactions leading to the induction of an immune response and also in the localization of lymphocytes in appropriate sites in the host. A major focus of our interest is to determine the molecular mechanisms by which lymphocytes control their migration to precise tissue locations. The movement of lymphocytes out of the blood stream is controlled by the expression of several surface receptor proteins that mediate adhesion to endothelial cells lining the blood vessels, the first step in migration into a tissue. Distinct membrane proteins cause adhesion (and hence traffic) to different anatomic sites. We have used biochemical methods (e.g., electrophoresis) and flow cytometry (FACS analysis) to characterize these receptors. After activation in tissue culture, T lymphocytes turn off (or down-regulate) expression of one specific adhesion molecule while up-regulating a series of different receptors. Thus, lymphocyte activation results in a series of biochemical events which lead to changes in intracellular recognition, adhesion, and cell traffic.

More recent experiments have examined the regulation of receptor expression in vivo. In lymph nodes adjacent to a skin transplant, a small subset of T lymphocytes modulate receptor levels, just as in the tissue culture model. By isolating them with the cell sorter, we showed that these cells are able to kill donor skin, and that they secrete large amounts of interferon, thus linking a characteristic adhesive phenotype to specific T cell killing and transplant rejection. Similar inflammatory cells are important in a model of virus-induced brain disease which leads to demyelination and paralysis.

These results suggest a model in which antigen-specific activation and differentiation of lymphocytes results in alteration in the array of surface adhesion receptors, with the loss of some and an increase in others. The net result of this would be to redirect the migration of lymphocytes away from lymphoid tissue and to the peripheral antigenic site, such as a transplant, where the cells could then mediate inflammation and graft rejection. Further experiments will examine the molecular genetic mechanisms by which these adhesion molecules are regulated and will determine their role in the host response to transplantation and malignancies. We are currently using recombinant DNA technology to create site-directed mutants of one of these receptors to determine the sites responsible for its regulation by protein kinases.