Monocyte-dependent induction of proliferation of human peripheral T cells by recombinant interleukin 2

The in vitro proliferation of human peripheral lymphocytes induced by interleukin 2 (IL2), a product of cDNA, cloned in E. coli has been studied. The maximal mitogenic signal is given by concentrations greater than or equal to 2.5 U/ml. Due to growth factor consumption, at least 10 U/ml are needed to maintain a logarithmic response until day 6. The anti-Tac antibody, directed against the IL2 receptor, effectively blocks this response, but we could not obtain a decrease of IL2-reactive cells by depletion of putative in vivo activated Tac+ cells, using this antibody and a fluorescence-activated cell sorter. Depletion of Leu7+ and Leu11b+ cells does not cause a decrease of the response, which indicates that the responding cells are not confined to the natural killer lineage. By simultaneous staining of cell-surface markers and DNA, the nature of the proliferating cell was determined. More than 90% of the dividing cells expressed HLA class II and the Tac antigen, whereas the lymphocyte populations, defined by the surface markers Leu2, Leu3, Leu4, Leu7 and Leu11b, were all represented in the dividing cells. The magnitude of the response was proportional to the number of monocytes present in the culture. Depletion of monocytes completely abrogated the response, whereas an increase in the number of monocytes to a 1:1 ratio with lymphocytes caused a 2-fold increase in proliferation. However, purified T cells do proliferate to IL2 when cultured in the presence of a supernatant that was harvested from a 2-day culture of adherent monocytes. The proliferation-inducing activity in the supernatant eluted with apparent molecular weights of 15 000 and 75 000 on an Ultrogel AcA-54 column. Therefore, we conclude that in vitro, in the presence of an IL1-like activity produced by monocytes, IL2 is mitogenic for a population of T cells.