Production of colony-stimulating factor(s) for granulocyte-macrophage and multipotential (granulocyte/erythroid/megakaryocyte/macrophage) hematopoietic progenitor cells (CFU-GEMM) by clonal lines of human IL-2-dependent T-lymphocytes.
Human T-lymphocyte lines that were selected for recognition of HLA-DR6 antigen and were dependent for growth in vitro on an added source of interleukin-2 (IL-2) were derived from the peripheral blood of normal individuals. Each was tested for production of a lymphokine(s) with properties of granulocyte-macrophage colony-stimulating factor (GM-CSF) using as target cells nonadherent cells from human long-term bone marrow cultures (LTBMC) or fresh marrow. Each of eight T-lymphocyte lines that were OKT3, OKT4, and HLA-DR positive produced GM-CSF that stimulated colony formation by both LTBMC cells and fresh marrow. Individually examined single-cell-derived bone marrow colonies growing in T-cell GM-CSF contained peroxidase-positive neutrophils, and macrophage-monocytes (GM-CFUc). Supernatant from a single-cell-derived T-cell clonal line designated F1 stimulated formation of granulocyte-macrophage colonies, megakaryocyte colonies, macroscopic erythroid bursts, and multipotential colonies containing erythroid cells, megakaryocytes, neutrophilic and eosinophilic granulocytes, and monocyte-macrophages (CFU-GEMM) in the presence of added erythropoietin. These data indicate that human IL-2-responsive T-lymphocytes produce lymphokine(s) that stimulate proliferation of primitive as well as committed hematopoietic stem cells, and implicate human T-lymphocytes in regulation of human multipotential hematopoietic stem cells in vivo.
D000954:Antigens, Surface / Q000032:analysis; D001854:Bone Marrow Cells; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology*; D006098:Granulocytes / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D008264:Macrophages / Q000166:cytology*; D008533:Megakaryocytes / Q000166:cytology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D007376:Interleukin-2