Role of interleukin 2 receptor β chain in initiating anti‐CD3 and interleukin 2‐induced proliferation of human resting T cells

We have examined the role of isolated interleukin 2 receptor (IL 2R) β chains expressed by human resting T cells in the early period of primary T cell activation induced by soluble OKT3 monoclonal antibody (mAb) and exogenous IL 2. In the initial 3‐day‐stimulation phase, high IL 2 concentrations were required, in association with soluble OKT3 mAb, to induce the formation of IL2R α/β heterodimers, while later, low IL2 concentrations were sufficient to promote cell growth. When added during the initial phase, TU27 mAb directed at the IL2 binding site of IL2R β chain substantially inhibited the appearance of functional high‐affinity IL2R. Lo‐Tact‐1 mAb directed at the IL2 binding site of the IL2R α chain had only a marginal effect. Strong induction of IL2R α mRNA occurred within 3 days upon OKT3 and IL2 stimulation even in the presence of Lo‐Tact‐1 mAb, but not in the presence of TU27 mAb. OKT3 alone failed to induce significant IL2R α gene transcription and that induced by IL2 alone was very weak. The constitutive expression of IL2R β mRNA was visualized in resting T cells. It remained at a rather stable level, at least during the initial stimulation period which was examined herein. Given the fact that OKT3 alone was ineffective in up‐regulating IL2R β mRNA expression and that pre‐incubation of the cells with OKT3 alone did not allow them to respond to high concentrations of IL2, it is highly probable that isolated IL2R β chains constitutively expressed by CD8+ T cells (the main reactive cells in this system) are primarily responsible for the initial interaction of IL2 with these cells. Such an interaction will result in the formation of high‐affinity IL2R and in the initiation of cell proliferation provided that a CD3‐derived co‐signal is simultaneously delivered to the cells.