title: Selective generation of erythroid burst-promoting activity by recombinant interleukin 2-stimulated human T lymphocytes and natural killer cells.
abstract: Because T lymphocytes and natural killer (NK) cells produce a variety of growth factors and interleukin 2 (IL2) modulates the activity of both, we assessed the ability of IL2 to stimulate human T cells and NK cells to produce hematopoietic growth factors detectable in clonogenic marrow culture. Human recombinant interleukin 2 (rIL2) added directly to cultures of human bone marrow that had been depleted of monocytes or depleted of both monocytes and T cells caused no significant alteration of myeloid (CFU-GM) or erythroid colony formation. Conditioned media harvested from rIL2-stimulated (greater than 100 U/mL) peripheral blood mononuclear cells, T cells, Leu-2 cells, and Leu-3 cells all had erythroid burst-promoting activity (BPA) but lacked myeloid colony-stimulating factor (GM-CSF) or CFU-GM-inhibitory activity. These T cells were IL2 receptor-negative, and the addition of anti-IL2 receptor monoclonal antibody (anti-Tac) to T cell cultures did not abrogate this IL2-stimulated BPA production. In addition, Percoll gradient-enriched, large granular lymphocytes (LGL) were separated by fluorescence-activated cell sorting into Leu-11+ (NK) cells and Leu-11- (low-density Leu-4+ T) cell fractions. rIL2 stimulated LGL, Leu-11+ and Leu-11- cells to produce BPA but not detectable GM-CSF or CFU-GM-inhibitory activity. Leu-11+ (NK) cells were Tac-negative from days 0 through 14 of culture. We conclude that rIL2 at high concentrations stimulated T cells, Leu-2 and Leu-3 cell subsets, LGL, and NK cells to produce BPA but not GM-CSF and that this stimulation may be mediated by an IL2 receptor distinct from Tac or by an epitope of the IL2 receptor not recognized by the anti-Tac antibody.
authors.affiliation: Department of Medicine, Stanford University Medical Center, Palo Alto, CA.
authors.forename: S
authors.initials: S
authors.lastname: Skettino
authors.forename: J
authors.initials: J
authors.lastname: Phillips
authors.forename: L
authors.initials: L
authors.lastname: Lanier
authors.forename: A
authors.initials: A
authors.lastname: Nagler
authors.forename: P
authors.initials: P
authors.lastname: Greenberg
mesh_terms: D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D006133:Growth Substances / Q000096:biosynthesis; D016298:Hematopoietic Cell Growth Factors; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008212:Lymphocyte Depletion; D008222:Lymphokines / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D007376:Interleukin-2; D008222:Lymphokines; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7