Human T lymphocyte activation in the presence of acute myelogenous leukaemia blasts; studies of normal polyclonal T cells and T lymphocyte clones derived early after allogenic bone marrow transplantation.
T cell clones (CD4+CD8-TCR alpha beta+gamma delta- derived from bone marrow transplant recipients were stimulated with phytohaemagglutinin (PHA) +interleukin-2 (IL-2) in the presence of irradiated (50 Gy) peripheral blood mononuclear cells (PBMC) derived from acute Leukaemia patients (leukaemic PBMC containing more than 95% blast cells). Leukaemic 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-stimulating factor (GM-CSF) tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) secretion]. Blockade of IL-1 effects by adding 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 cytokine 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 non-irradiated leukaemic PBMC. When leukaemic PBMC derived from 18 acute myelogenous leukaemia patients were cultured with PHA and cells from a polyclonal T cell line, increased concentrations of the T cell cytokines IFN gamma and IL-4 were detected for all patients. We conclude that T cell activation resulting in proliferation and a broad cytokine response can take place in the presence of excess acute myelogenous leukaemia blasts.
Bruserud
O
O
Medical Department B, Haukeland University Hospital, Bergen, Norway.
Pawelec
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000938:Antigen-Presenting Cells / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000276:immunology* / Q000601:surgery; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology / Q000528:radiation effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D010835:Phytohemagglutinins