Effects of interleukin‐2 and interleukin‐2‐activated cells on in vitro myelopoiesis

• Published in: Clinical and experimental immunology Vol. 81; no. 3; pp. 459 - 465
• Main Authors: CLERIGUE, M., PISA, P., TSAI, L., HANSON, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-1990; Blackwell
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Bone Marrow Cells; Colony-Forming Units Assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocytes - cytology; haematopoiesis; Hematopoiesis; Hematopoietic Stem Cells - cytology; Humans; Immunobiology; Interferon-gamma - biosynthesis; Interleukin-2 - pharmacology; interleukin‐2; Killer Cells, Lymphokine-Activated - metabolism; Killer Cells, Lymphokine-Activated - physiology; Lymphokines, interleukins ( function, expression); lymphokine‐activated killer cells; Macrophages - cytology; Recombinant Proteins - pharmacology; Regulatory factors and their cellular receptors; Tumor Necrosis Factor-alpha - biosynthesis; Human; Cell culture; Cytokine; In vitro; Biological activity; Interleukin 2; Cell population; LAK cell; Bone marrow; CFU-GM-Cell; Inhibition; Myelopoiesis; Mechanism of action
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.1990.tb05356.x

SUMMARY
Lymphokine‐activated killer (LAK) cells from human peripheral blood mononuclear cells cultured with recombinant interleukin‐2 (IL‐2) have been used clinically in adoptive immunotherapy for cancer patients. To study the influence of LAK cells and IL‐2 on haematopoiesis, an in vitro assay system for colony formation of granulocyte‐macrophage progenitor cells (GM‐CFC) was used. LAK cells from cultures of either human peripheral blood (PB) or human bone marrow (BM) mononuclear cells were both inhibitory to allogeneic BM‐derived GM‐CFC. Inhibitory activity could be transferred with supernatants from co‐cultures of LAK cells and BM targets, but also from the IL‐2 activated PB‐ or BM‐derived cells alone. The inhibitory activity from the initially non‐cytotoxic/non‐inhibitory BM population was rapidly induced by IL‐2 activation, and preceded the generation of cytotoxic LAK cells in the culture. These experiments show that inhibition of haematopoietic progenitor cells by IL‐2 is not dependent on generation of cytotoxic LAK cells, but rather the result of IL‐2‐induced cytokine production. We conclude that the synergistic action of interferon‐gamma (IFN‐γ) and tumour necrosis factor‐alpha (TNF‐α) may contribute to inhibition, but that also other cytokines are responsible for the observed inhibition of BM‐derived GM‐CFC.