Leukemia cell lines can replace monocytes for mitogen-induced T-lymphocyte responses: this accessory function is dependent upon their differentiation stage.
Highly purified peripheral T lymphocytes do not proliferate in response to phytohemagglutinin A or concanavalin A, unless adherent HLA-DR+ monocytes are added as accessory cells. The accessory function (AF) of monocytes is mediated through the release of interleukin-1 (IL-1). We here report that cells from three human leukemic lines--K562, HL-60, and U-937--could exert AF and efficiently replace monocytes in a 72-hr mitogen-stimulated proliferation assay. This AF was clearly related to precise maturational stages of these cells, since the hematopoietic precursor K562 cells spontaneously exerted high AF but lost this property when treated with differentiation inducers such as sodium butyrate or phorbol 12-myristate 13-acetate (PMA). On the other hand, untreated HL-60 and U-937 cells exhibited no spontaneous AF, but they acquired this function when induced to differentiate either along the granulocytic pathway (dimethyl sulfoxide-treated HL-60 cells) or along the monocytic pathway (PMA-treated HL-60 and U-937 cells). Supernatants from PMA-triggered K562 or HL-60 cells allowed the proliferative response of murine thymocytes to phytohemagglutinin A and were therefore shown to contain IL-1. Analysis of phenotypical markers showed that AF and IL-1 production were not restricted to cells of the monocytic lineage. No HLA-DR antigen could be detected on K562 and HL-60 cells. Thus, the expression of HLA-DR antigens is not required for AF and IL-1 production in response to mitogens. Human leukemia cell lines could provide useful sources of human IL-1.
D002454:Cell Differentiation; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D008213:Lymphocyte Activation; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology*; D008934:Mitogens; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D008934:Mitogens; D004121:Dimethyl Sulfoxide