We are defining the cells and molecules involved in the regulation and effecting of immune responses, including those against tumors. We focus on the function of three distinct classes of lymphocytes, the antibody producing B lymphocytes, the effector T lymphocytes, and the regulator T lymphocytes. Effector T lymphocytes have heterodimeric protein receptors recognizing MHC gene products or foreign antigens assocated with such cell surface antigens. Their effector function is mediated by release of soluble, biologically active, nonantigen-specific molecules. Tumor cells are frequently susceptible to these products. The activity of these cells is under the control of the complex circuitry of regulatory T cells. Our basic strategy is to identify such cells by means of cell surface molecular structures recognized by monoclonal antibodies. These antibodies are, ideally, directed against the cell surface antigen receptors and cell free biologically active products of such cells. Such antibodies have been prepared and have been shown to mediate profound effects on the immune response in vivo, including the immune response to tumors. To further define these products, we are cloning the genes and encoding them. Our future studies involve the further generation of clonal and recombinant DNA sources of such immunoregulatory molecules. Second, we would like to manipulate the immune response in vivo using our molecular and antibody probes in order to determine the role of the immune response and its regulation tumor cell growth. Third, we will use these probes to measure the regulatory elements of the immune response in in vitro and in vivo antibody and cell mediated immune responses. These studies should allow a clearer picture of the immunoregulatory apparatus which may suppress effective anti-tumor immunity. Of greatest importance, our ability to manipulate this response may allow new avenues in the regulation of tumor growth. (LB)
Showing the most recent 10 out of 73 publications
