Clinical and theoretical implications of experimental bone marrow transplantation.
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Biomedical subjects
Publications and source records attributed to B Vitale.
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The immunological capacity of lymphoid cells from mice rendered tolerant to high and low doses of BSA was investigated. The tolerance was induced by multiple injections of high and low doses of antigen through the period of 30 days. Lymph node and bone marrow cells from tolerant animals were transferred into lethally irradiated syngeneic recipients. After 10 days, when lymphoid organs of the recipients were repopulated with the injected cells, challenge injection of the same antigen incorporated into complete Freund's adjuvant was given. The immune response of the transferred cells in the recipients was evaluated by analysis of the specific antibodies in the sera. Lymphoid cells from donors rendered toloerant with high doses of antigen recovered their reactivity 20 days after the transfer to the level of reaction of normal cells. Lymphoid cells from donors receiving multiple injection of low doses of BSA remained tolerant after the transfer through the entire observation period. According to the cellular events in the donors during the period of tolerance induction, and the behaviour of the transferred lymphoid cells in the new recipients, it seems possible that tolerance induced with high doses of BSA corresponded to the B-cell tolerance, while low doses of antigen most likely induced tolerance of T-cell population. The possible cellular mechanisms of B and T-cell tolerance were discussed.
The distribution of labeled lymph node cells, causing an acute GvH reaction in lethally irradiated allogeneic recipients, was studied. Lymph node cells of C57BL mice were labeled with 51Cr and injected into lethally irradiated: a) C57BL mice, b) CBA mice, c) CBA mice sensitized to C57BL antigens prior to irradiation, d) CBA mice splenectomized before irradiation. Two more experimental situations were studied in which C57BL donors of lymph node cells were: e) presensitized to CBA antigens, or f) deprived of T-lymphocytes. The amount of radioactivity was determined in the whole body, blood, liver, spleen, subcutaneous lymph nodes, lungs, femora and kidneys of the irradiated recipient at regular intervals from the time of injection to the 120th hour after it. We found that living cells lodged predominantly in the spleen and the lymph nodes, while dead and dying cells accumulated in the liver. Other organs contained very small amounts of radioactivity. All the results point to the primary role of the spleen in the acute graft-versus-host reaction.
Cellular events in the spleen during the development of acute GvH reaction in lethally irradiated recipients of allogeneic lymphocytes may be divided into 6 interrelated processes: (1) entering and lodging in the spleen of about 17% of inoculated cells which forms the compartment of potentially reactive cells; (2) transformation (recruitment) of about 30% of cells lodged in the spleen into large pyroninophilic cells (LPC), a process lasting about 12-16 hr; (3) proliferation of recruited LPC by five successive divisions with a Tc of about 12 hr; (4) transformation of LPC into non-LPC; (5) proliferation of non-LPC by one division, with a Tc of about 8 hr; and (6) migration of mature immunologically active cells from the spleen. The last process correlates well with the concomitant appearance of lymphocytes in the peripheral blood (killer cells) and with the time of acute death among inoculated mice.
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