Antitheta-sensitive regulatory cell (TSRC) and hematopoiesis: regulation of differentiation of transplanted stem cells in W/Wv anemic and normal mice

The macrocytic anemia of the W/Wv mouse can be cured by the injection of normal littermate bone marrow cells into nonirradiated recipients. In addition to the stem cell requirement for this cure, we describe a cell type sensitive to treatment in vitro with antitheta serum and complement that appeared to be required for a cure. The mechanism of action of this antitheta-sensitive regulatory cell (TSRC) involves its effect on the pluripotent stem cell. Cells from the thymus of normal littermates, when infused with bone marrow cells from a normal donor, increase the number of spleen colonies found in nonirradiated W/Wv recipients. While depletion of the TSRC does not appear to be cytotoxic to the stem cell, it alters the differentiation pathway of cells seeding in the spleen following transplant. There is a shift from predominantly erythroid to granuloid microscopic colonies following such treatment. Thymocytes from normal but not anemic donor animals will cooperate with the stem cell from T cell-depleted marrow to produce predominantly erythroid colonies and, furthermore, will cure the anemic mouse. The number of thymocytes required is exceedingly small (103-104); the “helper” function is not destroyed by irradiation in vitro or in vivo, and initial cell-to-cell contact appears to be required (TSRC and stem cell) for cure of the anemic W/Wv recipients.