HUMAN T-LYMPHOCYTE ACTIVATION IN THE PRESENCE OF ACUTE MYELOGENOUS LEUKEMIA BLASTS - STUDIES OF NORMAL POLYCLONAL T-CELLS AND T-LYMPHOCYTE CLONES DERIVED EARLY AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

T cell clones (CD4(+)CD8(-)TCR alpha beta(+)gamma delta(-)) derived fr om bone marrow transplant recipients were stimulated with phytohaemagg lutinin (PHA) +interleukin-2 (IL-2) in the presence of irradiated (50 Gy) peripheral blood mononuclear cells (PBMC) derived from acute leuka emia patients(leukaemic PBMC containing more than 95% blast cells). Le ukaemic PBMC could function as accessory cells during mitogenic T cell activation resulting in both T cell proliferation and a broad T cell cytokine response [IL-3, IL-4, IL-10, granulocyte/macrophage-colony-st imulatin factor (GM-CSF) tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) secretion]. Blockade of IL-1 effects by a dding IL-1 receptor antagonist together with PHA+IL-2+leukaemia blasts increased T cell proliferation, whereas IL-6-neutralizing antibodies did not alter T cell proliferation. A qualitatively similar T cell cyt okine response and a similar cytokine profile (highest levels detected for GM-CSF and IFN gamma) were detected when normal polyclonal T cell lines were stimulated with PHA in the presence of nonirradiated leuka emic PBMC. When leukaemic PBMC derived from 18 acute myelogenous leuka emia patients were cultured with PHA and cells from a polyclonal T cel l line, increased concentrations of the T cell cytokines IFN gamma and IL-4 were detected for all patients. We conclude that T cell activati on resulting in proliferation and a broad cytokine response can take p lace in the presence of excess acute myelogenous leukaemia blasts.