Effect of tritiated thymidine and 5-bromodeoxyuridine on development of immunologically competent lymphocytes.

Results of the present experiments suggest that dividing cells in rat bone marrow can generate lymphocytes capable of initiating a systemic graft--host reaction. In these experiments, Lewis bone marrow cells were incubated with either tritiated thymidine ([H]thymidine) or 5-bromodeoxyuridine (BUDR)—agents which inhibit cell proliferation. Bone marrow cells prepared in this way and injected into an intermediate (Lewis×DA)F host were unable to proliferate and mature into circulating immunologically competent lymphocytes. Concentrations of [H]thymidine and BUDR which inhibited the development of putative lymphocyte precursors in bone marrow had no obvious effect on the immunological performance of thoracic duct lymphocytes. Lewis lymphocytes, cultivated in medium containing these agents, caused a vicious graft--host reaction in X-irradiated (Lewis×BN)F hybrid rats. The results strengthen the view that [H]thymidine and BUDR exert their inhibitory effect on replicating lymphocyte precursors and not on long-lived members of the circulating lymphocyte pool.