HUMAN T-LYMPHOCYTE ACTIVATION IN THE PRESENCE OF ACUTE MYELOGENOUS LEUKEMIA BLASTS - STUDIES OF ALLOSTIMULATED INTERFERON-GAMMA SECRETION

Normal peripheral blood mononuclear cells (PBMC responders) were cultu red together with non-irradiated allogeneic PBMC (more than 95% leukae mia blasts) derived from patients with acute leukaemia (referred to as leukaemic PBMC stimulators). Cytokine secretion was determined as cyt okine concentrations in supernatants. Both normal PBMC and enriched CD 4(+) and CD8(+) T cells responded to allostimulation with interferon ( IFN gamma) secretion. Interleukin-1 (IL-1) receptor antagonist and IL- 2-neutralizing antibodies decreased IFN gamma secretion. Exogenous IL- 1 beta, IL-2 and IL-7 increased allostimulated IFN gamma secretion, wh ereas decreased levels were seen in the presence of IL-6, IL-10 and gr anulocyte-colony-stimulating factor (G-CSF). During allorecognition IF N gamma-neutralizing antibodies decreased acute myelogenous leukaemia (AML) blast secretion of G-CSF. We conclude that (i) both CD4(+) and C D8(+) T cells show allostimulated cytokine secretion in response to al logeneic stimulator cells containing a dominating population of native , cytokine-secreting leukaemia blasts, and (ii) IFN gamma released dur ing this response can modulate the function of allogeneic AML blasts.