Nuclear Medicine Technology Health Applications and Other Project Title: Lymphocytopoiesis and Transpiantation Immunology 16. Technical Progress in FY 1973: (Cont'd) Peyer's patch, and bone marrow. RX-01-03-(d) Lymphocyte concentration in the blood declined continuously during ECIB. Repletion of lymphocytes began a. few days after cessation of ECIB and continued for the duration of the study. Complete recovery, however, was not achieved by 2 months after termination of ECIB. Changes similar to those seen in blood lymphocyte concentration (decrease and recovery) were also observed in the thoracic duct lymph. The spleen, lymph nodes, thymus, and Peyer's patches showed various degrees of lymphocyte depletion during ECIB. Lymphocyte concentration in the bone marrow remained constant. Within the two-month experimental period, the thymus, lymph nodes and Peyer's patches recovered completely while the spleen, despite showing some recovery, remained partially depleted for the entire period. Following cessation of ECIB, the lymphocyte concentration in bone marrow increased, reaching a; level above the controls by day 4. Thereafter it returned to the level of the mean sham control groups and appeared to remain below this level for the entire period of the study. During ECIB an increase in the flash labeling index of the dividing population of lymphocytes was noticed in the bone marrow, Peyer's patches, blood and thoracic duct lymph. increase was most marked in the bone marrow. The The peak level of the labeling index of the bone marrow was attained on day 4 following cessa- tion of ECIB, also peaked. the time at which the lymphocyte concentration of bone marrow Thymus and spleen did not show any appreciable change in the labeling index as a result of ECIB. An increase in labeling index of the dividing population of lymph node lymphocytes was observed during ECIB and sham ECIB. The observation that ECIB-induced lymphocytopenia initiated a stimulatory signal for increased proliferative activity of lymphocytes in the bone marrow is new and exciting and may shed light on one of the original objectives of ECIB, namely, and to show whether partial depletion of lymphocytic tissues triggers proliferation within some segment of the lymphocytic system. Whether this increased pro- liferation is in response to increased cell destruction, or to a mechanism that senses a decrease in size of lymphocyte pools in blood or tissues is not known. Earlier studies had shown that peripheral lymphocyte depletion results in an initial, temporary depletion in the thymus during ECIB. The thymus is known to be repopulated by cells originating in the bone marrow after fatal irradiation. These facts, and the increased proliferative activity observed in bone marrow, suggest that there might be a feedback loop from the thymus to the marrow, stimulating marr@M production to replete the thymus. “Bering the preceding studies, the lymphocyte count/unit volume of thoracic duct lymph continued to fall, reaching the lowest level a few days after cessation of ECIB. To study this further, thoracic ducts were cannulated and arteriovenous shunts cstablished in calves. One calf was subjected to intermittent ECIB and the other received intermittent sham (See Continuation Sheer) [119231 RX-73