Amplification of IL-2-driven T cell proliferation by recombinant human IL-3 and granulocyte-macrophage colony-stimulating factor.

Abstract

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.