In vitro stimulation of cell-mediated cytotoxicity by acute leukaemias

Abstract

Acute leukaemias stimulated proliferative and cell-mediated cytotoxic (CMC) responses in vitro in normal (unprimed) lymphocytes. Proliferation was detected by increases in viable cell counts and [3H]dT incorporation in mixed lymphocyte-leukaemia-cell cultures. CMC detected on cultured cell-line targets (CCL) including K562 was generally much stronger than on fresh leukaemia cells, and correlated with stimulation of [3H]dT uptake in the responding lymphocytes. Leukaemias which were resistant as targets to CMC were able competitively to inhibit CMC on K562, though not as efficiently as blocking by K562 itself. With one leukaemia, blocking of CMC increased as the level of CMC on K562 was amplified by greater numbers of stimulating cells in the sensitization phase. This suggests that in certain cases blocking of effector cells by acute-leukaemia cells may depend upon the state of activation of the effector cells. Lymphocytes from a leukaemia patient in remission, treated with allogeneic leukaemia-cell immunotherapy and stimulated in vitro with immunizing leukaemia cells, developed strong anti-leukaemic CMC. A non-immunized patient's lymphocytes did not respond in this way, despite comparable levels of CMC on K562 in both patients. Dual stimulation of unprimed normal lymphocytes and remission lymphocytes with allogeneic or autologous leukaemias and various cell lines, amplified anti-leukaemic CMC, but did not markedly alter CMC or CCL. These data do not formally exclude the mediation of in vitro-stimulated anti-leukaemic CMC by NK-like cells, but suggest that such effector cells differ qualitatively from NK-like cells detected in the absence of anti-leukaemic CMC.