The proposed studies are of cell-mediated immunity in humans to leukemia and lymphoma associated antigens and to antigens associated with cells infected with Herpes viruses that cause recurrent or latent infection. The specific aims of the leukemia-lymphoma project are to sensitize lymphocytes from leukemia and lymphoma patients (or from their HLA identical siblings) to antigens associated with autologous or syngeneic leukemia or lymphoma cells by various in vitro manipulations in order to generate cytotoxic lymphocytes specifically directed against these cells; and to determine whether lymphoma or leukemia cells from different patients with similar types of disease (based on cell morphology, special staining characteristics and immunological cell surface markers) share common target cell antigens against which the cytotoxic lymphocyte response is directed. The aims of the studies on cell-mediated immunity to Herpes viruses are to determine whether stimulation of lymphocytes from individuals with a past history of exposure to Herpes Simplex virus type 1 (HSV-1), with HSV or HSV-infected cells leads to the generation of cytotoxic lymphocytes directed against antigens expressed on HSV-infected cells; to compare the cytotoxic responsiveness of lymphocytes from normal individuals and individuals with recurrent herpes Labialis; and in addition to determine whether in vitro generated cytotoxic mouse lymphocytes directed against HSV-infected cells can adoptively transfer immunity to lethal HSV infections in mice without causing adverse side effects. Similar studies on cell-mediated immunity in humans to Cytomegalovirus and Herpes Varicella-zoster virus will be initiated that are designed to generate large numbers of specifically cytotoxic lymphocytes directed against cells infected with these Herpes viruses.