Evaluation of antithymocyte globulin for human bone marrow transplantation. III. Effect of antithymocyte globulin treatment on t cell precursors.

The effect of antithymocyte globulin (ATG) treatment on T cell precursors was investigated in an in vitro model of E rosette induction by thymic factors. Approximately 8% of bone marrow mononuclear cells can be induced to form E rosettes following incubation with thymosin or with conditioned medium from cultured thymic epithelium (CM-CTE). Treatment of bone marrow mononuclear cells with ATG alone markedly reduced but did not eliminate precursors of E rosette-forming cells (E-RFCs), whereas treatment with ATG and complement completely inhibited these bone marrow E-RFC precursors. E-RFCs already present in peripheral blood and bone marrow were completely inhibited by treatment with ATG alone. E-RFCs induced by treatment of bone marrow cells with thymosin or CM-CTE were also completely inhibited by ATG alone. These data indicate that bone marrow precursors of E-RFCs are less sensitive to ATG inhibition than are peripheral blood and bone marrow E-RFCs. When bone marrow precursor T cells are induced to become E-RFCs by the treatment with thymic factors, they acquire comparable sensitivity to ATG. A similar disparity in sensitivity to ATG treatment was observed when ATGs absorbed with human fetal liver cells or granulocytes were studied. These data suggest that ATG treatment of bone marrow cells may have different effects on mature and precursor T cells. It is important to consider these factors in attempts to use ATG treatment in clinical bone marrow transplantation trials.