The role of allogeneic cells in the stimulation of cell-mediated cytotoxicity to leukaemia cells. A family study

Abstract

Allogeneic lymphocytes can stimulate cell-mediated cytotoxicity (CMC) in lymphocytes from leukaemia patients against autologous leukaemia target cells. We have compared the capacity of different allogeneic lymphoid cells to stimulate CMC to fresh (i.e., patient) and cultured (MOLT 4, K562) leukaemic target cells in lymphocytes from an acute leukaemic patient and his HLA-identical siblings. Allogeneic lymphoid cells, and particularly a lymphoblastoid cell line, were effective in stimulating CMC to leukaemia targets. In some instances, however, leukaemia cells derived from the patient, mixed with allogeneic lymphoid cells stimulated synergistic CMC to the patient's leukaemia. We also found that the patient's leukaemia cells alone were able to stimulate CMC in HLA-identical sib lymphocytes to fresh and cultured leukaemia targets. Extra specificities on fresh leukaemia cells were revealed when these cells induced unpredicted CMC on normal lymphocyte targets when added to mixed lymphocyte cultures (MLC) between related and unrelated lymphocytes. Cytotoxic lymphocytes generated in MLC against the patient's HLA antigens were absorbed by monolayers of lymphocytes and leukaemia cells of the same HLA type as the patient, leaving residual CMC to fresh (patient) and cultured (K562) leukaemia target cells. In addition, CMC to the patient's leukaemia cells, stimulated in lymphocytes from the patient's HLA-identical sib by allogeneic cells, was absorbed by a monolayer of these allogeneic cells. This suggests cross reactivity between determinants on the leukaemia and allogeneic lymphocytes. The results of this study are consistent with expression of 'leukaemia antigen', which are not restricted to leukaemia cells but may also be expressed on lymphocytes.