The research of this laboratory is directed at understanding mechanisms of tissue and growth-specific gene regulation in T lymphocytes. Lymphocyte metabolism and effector function expression are regulated by antigen/mitogen and lymphokine binding to cell surface receptors. We are investigating the physiological consequences of mitogen and lymphokine mediated signals by isolating and characterizing genes which are transcriptionally regulated by these events. We expect that genes induced within a few hours after antigen or mitogen activation of lymphocytes will be fundamentally important for the initiation of proliferation and effector function expression in these cells. We have shown that the c-myc oncogene is transcriptionally induced as early as one hour after the activation of murine B cells with LPS or T cells with Con A. Two additional proto-oncogenes, c-myb and c-fos, are similarly regulated by both IL-2 and PHA or PHA only, respectively, in human T lymphocytes. Thus, three oncogenes are members of the gene family regulated by mitogen binding to the surface of lymphocytes. The identification of additional members of this inducible gene family has been made utilizing PHA stimulated human peripheral blood T cells and subtraction cDNA cloning methodology. An additional gene sequence, the T cell receptor Beta chain, that encodes a product fundamental for the manifestation of effector function in T cells currently is being analyzed with regard to DNA sequences and trans-activating factors that determine expression.
