Production of erythroid burst-promoting activity (BPA) and granulocyte-monocyte colony-stimulating activity (GM-CSA) by isolated human T-lymphocyte subpopulations.
T-lymphocytes and monocytes are prominent among the classes of normal human cells that have been implicated in the production of the hemopoietic growth factors granulocyte-macrophage colony-stimulating activity (GM-CSA) and erythroid burst-promoting activity (BPA). To investigate the nature of the cooperativity that occurs during the elaboration of these growth factors by activated T-lymphocytes and monocytes in vitro, and to define the subsets of T cells involved in this response, we studied the production of GM-CSA and BPA by populations of T-lymphocytes isolated by fluorescence-activated cell sorting, using the monoclonal antibodies OKT3, OKT4, and OKT8. When OKT3+, OKT4+, or OKT8+ cells were incubated for five days in liquid suspension cultures, their production of GM-CSA and BPA was undetectably low. When 5% autologous monocytes were added to the cultures, no increase in the secretion of either of these classes of growth factors was noted. In the presence of concanavalin A (Con A), measurable quantities of both GM-CSA and BPA were elaborated by all three populations of T cells in the absence of monocytes; however, when autologous monocytes were added to the Con A-stimulated T cells, the secretion of both GM-CSA and BPA was markedly enhanced. In addition, we found that supernates of unfractionated T cells incubated with Con A contained not only GM-CSA and BPA but also a potent inhibitor(s) of BPA that could be demonstrated by dilution of the media and removed by gel filtration. In contrast, no inhibitor of GM-CSA was found. By molecular sieve chromatography of the supernates, GM-CSA and BPA coeluted as a single peak. However, the two biologic activities could be separated on the basis of heat stability, since GM-CSA proved to be heat labile whereas BPA did not. Our data indicate that GM-CSA and BPA derived from human T cells are similar in their apparent molecular weights and in the pattern of their production in suspension cultures in response to lectin stimulation. The secretion of both GM-CSA and BPA by Con A-stimulated T cells is facilitated by the presence of autologous monocytes, and is not restricted to either the OKT4- or the OKT8-defined subset.
D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000302:isolation & purification; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood*; D008222:Lymphokines / Q000096:biosynthesis* / Q000302:isolation & purification; D012016:Reference Values; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology / Q000502:physiology*; D019714:Tissue Inhibitor of Metalloproteinases
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D008222:Lymphokines; D019714:Tissue Inhibitor of Metalloproteinases