T cell triggering by lectins. II. Stimuli for induction of interleukin 2 responsiveness and interleukin 2 production differ only in quantitative aspects.

Abstract

We have investigated the requirements for lectin-induced proliferation of highly purified human T cells. To study activation, independent of growth factor production, we cultured the cells in the presence of an excess of interleukin 2 (IL2), which was a product of cDNA cloned in E. coli. In the presence of IL2, the same cooperative effect of lectin and accessory cells was found that we have previously described for IL2 production. Thus, analogous to induction of IL2 production, the acquisition of responsiveness to IL2 can be completely monocyte dependent, but a 10-fold increase in lectin concentration completely abolishes the requirement for accessory cells. Furthermore, two stimuli (IL 1 and phorbol myristate acetate), which are able to replace monocytes at the level of IL2 production, also induce responsiveness to IL2 under accessory cell-dependent conditions. Thus, very similar conditions are required for proliferation and for the induction of IL2 production. There is only a quantitative difference: proliferation of cells in the presence of exogenous IL2 occurs already at low lectin concentrations, whereas IL2 production and consequently proliferation in the absence of exogenous IL2 requires higher lectin concentrations. At high lectin concentrations, when IL2 production has become the only limiting factor, purified T cells cannot be induced to proliferate in the absence of exogenous IL2 because the lectin concentration that induces IL2 production independent of accessory cells inhibits mitogenesis. However, after addition of thiols to the medium, which enhances the IL2 production, a very narrow range of lectin concentration can be found which is just below toxic values and still high enough to induce IL2 production in the absence of accessory cells. Under these conditions, accessory cells are no longer a prerequisite for lectin-induced T cell proliferation.