Amplification of IL-2-driven T cell proliferation by recombinant human IL-3 and granulocyte-macrophage colony-stimulating factor.
Two recombinant human preparations of CSF, namely granulocyte-macrophage-CSF (GM-CSF) and IL-3 (multi-CSF), were tested for their ability to stimulate the growth of human freshly separated and in vitro activated lymphocytes. Both CSF independently induced short term proliferation in unfractionated PBL and lectin-stimulated T cells. Despite the great variability among different donors in the magnitude of lymphocyte response to the two growth factors, IL-3 at suboptimal concentrations (10 U/ml) consistently induced a higher proliferative response than did GM-CSF at suboptimal concentrations (5 ng/ml) in all of the preparations tested. When used in combination with IL-2, GM-CSF and, especially, IL-3 significantly potentiated the proliferative responses induced by IL-2 in both unstimulated and mitogen-activated lymphocytes. Dose-response curves using increasing concentrations of IL-2 and IL-3 and isobologram analysis of these interactions revealed a clear synergy of action between the two growth factors in inducing proliferation of unfractionated PBL, purified T cells, mitogen-activated lymphocytes, and alloantigen-stimulated T cells. In addition to enhancing the short term responsiveness to IL-2, GM-CSF and, especially, IL-3 drastically potentiated the long term growth of non-activated human lymphocytes and of lectin- or Ag-activated T cells in the presence of IL-2. Immunofluorescence analysis indicated a higher expression of activation Ag (anti-Tac receptors and HLA class II Ag) in cultures incubated in the presence of IL-3 either alone or in conjunction with IL-2. The overall data indicate that human GM-CSF and IL-3 can support the growth of cells within the lymphoid lineage and exert potent amplifying effects on IL-2-induced T cell growth in vitro.
Santoli
D
D
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Clark
S C
SC
Kreider
B L
BL
Maslin
P A
PA
Rovera
G
G
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000954:Antigens, Surface / Q000032:analysis / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007376:Interleukin-2; D007377:Interleukin-3; D007519:Isoantigens; D008934:Mitogens; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor