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.
D002460:Cell Line; D006854:Hydrocortisone / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*; D013936:Thymidine / Q000378:metabolism
D007376:Interleukin-2; D007975:Leukotriene B4; D013936:Thymidine; D006854:Hydrocortisone