Leukotriene B4 causes proliferation of interleukin 2-dependent T cells in the presence of suboptimal levels of interleukin 2

We have recently found that endogenous leukotriene B₄ (LTB₄) production is a necessary component of mitogen-stimulated T-cell proliferation. In this report, we address the relationship between LTB₄ and interleukin 2 (IL-2) in stimulating proliferation of IL-2 responsive T cells. We employed an IL-2 responsive T-cell line, HT-2 and also human peripheral blood T cells rendered IL-2 responsive by culture with phytohemagglutinin (PHA). In the presence of concentrations of IL-2 that resulted in suboptimal stimulation of HT-2 cells (5-20% of maximum proliferation), LTB₄ at 10^-8 or 10^-10 M produced a several-fold increase in [³H]thymidine incorporation, resulting in levels of [³H]thymidine incorporation that were comparable to those produced by HT-2 cells stimulated with optimal concentrations of IL-2. Similar results were obtained with the peripheral blood T cells. Leukotriene C₄, prostaglandin E₂ (PGE₂), and arachidonic acid did not share with LTB₄ the ability to stimulate proliferation of HT-2 cells. Hydrocortisone and nordihydroguairetic acid (NDGA), drugs which block endogenous LTB₄ production in cell cultures inhibited [³H]thymidine incorporation of HT-2 cells stimulated by suboptimal but not optimal levels of IL-2. This inhibition could be overcome by the readdition of LTB₄ to the cultures. Thus, LTB₄ in physiologic concentrations (10^-10 M) can substitute for IL-2 in stimulating proliferation of IL-2 responsive T cells, provided that some IL-2 is present in the culture. Endogenous LTB₄ may act synergistically with endogenous IL-2 in promoting T-cell proliferation.