Receptor-specific inhibition of bone marrow erythropoiesis by recombinant DNA-derived interleukin-2.
Interleukin-2 (IL-2) induces differential secretion of lymphokines by IL-2 receptor (IL-2R)-positive and IL-2R-negative T cells. We studied T cell IL-2R-specific modulation of adult bone marrow erythropoiesis by recombinant IL-2 (rIL-2). I3-2R were induced by CD3 T cell surface determinant-triggering and analyzed by cytofluorography. Bone marrow monocyte and T cell-depleted (NAB-T) target cells were assessed for early erythroid progenitor expression (BFU-E) in the presence of 0 to 10(3) U/mL of rIL-2, rIL-2 had no significant effect on BFU-E expression in the absence of T cells or in the presence of IL-2R-negative T cells. rIL-2 caused a dose-dependent inhibition (75% to 90%) of BFU-E in the presence of autologous IL-2R-positive T cells. The addition of anti-IL2-receptor antibody to cultures containing rIL-2 plus IL-2R-positive T cells entirely abrogated rIL-2-mediated inhibition of BFU-E. In the presence of rIL-2 (10(2) U/mL) production of interferon gamma (IF-gamma) by adult marrow CD3-triggered IL-2R-positive T cells was increased 37- to 125-fold compared to IL-2R-negative T cells. rIF-gamma caused a dose-dependent (88% +/- 17% at 10(3) U/mL) inhibition of adult BFU-E in the presence of CD3-triggered autologous T cells. rIL2-mediated inhibition of adult BFU-E in the presence of IL-2R-positive T cells was partially abrogated (52% +/- 16%) following addition of monospecific IF-gamma antibody. These results demonstrate (a) rIL-2 modulation of adult marrow erythropoiesis is selectively dependent upon both the presence or absence of autologous T cells and the IL-2R status of these T cells; and (b) rIL-2-induced inhibition of adult marrow erythropoiesis is mediated in part by release of IF-gamma from IL-2R-positive T cells.
D000328:Adult; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D001854:Bone Marrow Cells; D002450:Cell Communication; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000648:ultrastructure
D000906:Antibodies; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma