Generation of cytotoxic lymphocytes in vitro against autologous human leukaemia cells.

Abstract

NORMAL lymphocytes cultured with allogeneic cells in one-way mixed leukocyte culture (MLC) respond proliferatively to the “lymphocyte-defined” (LD) antigens and subsequently cytotoxic cells are generated against the target antigens on the stimulating cells1. In contrast, when responding lymphocytes are cultured with stimulating lymphocytes that differ with respect to target antigens but not LD antigens, proliferative and cytotoxic responses are not easily generated; the addition of a second stimulating cell differing from the responding cell with respect to LD antigens in a ‘three-cell’ experiment allows the generation of cytotoxic lymphocytes directed against target antigens1–4. Consistent with results of others5–9, we have detected low but significant MLC responses after culturing remission lymphocytes with irradiated autologous leukaemia cells; however, cytotoxic lymphocytes were not generated. Using the ‘three-cell’ approach, where remission lymphocytes, irradiated leukaemia cells and irradiated allogeneic stimulating cells were cocultured, we have generated lymphocytes specifically cytotoxic for autologous human leukaemia cells.