Nuclear Medicine Technology and Other Health Applications Project Title: Lymphocytopoiesis 14, Scope: <(Cont'd) and Transplantation Immuno logy RX-01-03- (d) leukemia; c) to establish the role of bone marrow and thymic-derived lymphocytes in other mammals than the mouse. The role of the lymphopoietic system in immunity is established. Present doctrine states: antigens are recognized by thymic (T) cells, transformation of bone marrow (B) cells is followed by proliferation and development of clones of B cells producing specific antibody. Factors regulating the proliferation of hemopoietic stem ceils (HSC) in the bone marrow and their differentiation into the lymphopoietic system as well as other cell lines are not understood. Through nucleic acid labeling with tritiated precursors, autoradiography, and the detection of specific antigens characteristic of the T lymphocyte, cell proliferation and migration are studied in an endeavor to characterize the kinetic model of lymphocytopoiesis and its regulation. B) Supplement to 200 Word Summary: DNA and RNA labeling of lymphocytes by radioactive precursors of nucleic acids is accomplished by: a) intravenous administration to the whole body; b) single organ perfusion in vivo; c¢) in vitro incubation; d) in vitro and in vivo techniques combined; and e) cross circulation of a labeled allogeneic animal or syngeneic twin with an unlabeled vartner. These techniques are applied: a) to estimate cell cycle times of various classes of lymphocytes; b) to study the influence of concentration of lymphocytes in blood and/or Lymph on cell cycle times and cell proliferation rates; c} to measure cell production in, and cell migration fron, individual lymphoid organs such as bone marrow, lymph nodes, spleen, and thymus; d) to study lymphocytopoiesis in animals deprived of major lymphoid organs; e) to characterize the mechanism by which agents such as heparin and B. pertussis cause lymphocytosis; f) to study the recirculation of allogeneic and syngeneic lymphocytes; and g) to measure the Life span of migrant cells from organs Labeled by perfusion. The thymus regulates in part the size of the circulating pool of lymphocytes. The influence of thymectomy on the sizes of the various lymphocytic pools is studied utilizing isotopic dilution and the depletion methods of extracorporeal irradiation of the blood (ECIB) and lymph (ECIL). The Ws be obeenan between the thymus and the bone marrow lymphocytes is sM§Fied by observing proliferation and antibody production in diffusion cham B containing mixtures of B and T cells. Regional organ perfusion of bot® marrow and thymus by radioactive isotopes is used to study in vivo the interaction of migrant B and T cells in lymph nodes and spleen. The proliferating and non-proliferating lymphoid cells are tagged with various radioisotopic labels to study their migration patterns, life span, (See Continuation Sheet) 1179226 RX-68