IL-2 abolishes fibroblast proliferation in long-term bone marrow culture by inhibition of an accessory cell

Addition of interleukin-2 (IL-2 (greater than 250 U/ml) during the first 3 d of long-term bone marrow culture (LTBMC) permanently abolished the fibroblast component of the stromal layer, even when IL-2 was removed after the 3 d culture period. When IL-2 was added at more than 72 h after initiation of culture, no effect was observed. Stromal growth in IL-2-treated culture was restored by addition of irradiated bone marrow, indicating that the IL-2 inhibited an accessory cell rather than the fibroblast directly. Accessory cells were shown to be necessary for fibroblast proliferation at low cell densities and were also inhibited by IL-2. The accessory cell effect could not be replaced by LTBMC supernatants or extracellular matrix. It is suggested that these observations are relevant to the suppression of haemopoiesis observed in patients receiving IL-2.