Leukotriene B4 augments interleukin-2 receptor-beta (IL-2R beta) expression and IL-2R beta-mediated cytotoxic...

Interleukin-2 can induce cytolytic activity in human peripheral blood lymphocytes and this activation is mediated by the beta chain of the interleukin-2 receptor-beta (IL-2R beta). Leukotriene B4 (LTB4) is a potent lipid inflammatory mediator which induces IL-2 and interferon-gamma (IFN-gamma) production from T cells. We examined the ability of LTB4 to modulate IL-2-induced cytolytic activity. Peripheral blood lymphocytes which had been preincubated for 24 hr in the presence of LTB4 responded to 100-fold lower concentrations of IL-2 with an augmentation of natural killer (NK) cell cytotoxic activity. Furthermore, incubation of lymphocytes with graded concentrations of LTB4 augmented the proportion of IL-2R beta+ cells. Peak activity was seen at 10 nM LTB4 and was comparable to that of PHA. By two-colour cytofluorometry, the increased expression of IL-2R beta was found predominantly on CD56+ cells and to a lesser extent on CD8+ cells, while CD4+ cells were unaffected. These observations were correlated at the messenger RNA (mRNA) level with increased IL-2R beta mRNA accumulation following stimulation of purified CD56+ and CD8+ cells with LTB4. CD56-, CD8- cells did not respond to LTB4 by increased IL-2R beta mRNA accumulation. Our data indicate, for the first time, that LTB4 can markedly increase the sensitivity of non-major histocompatibility complex (MHC)-restricted cytotoxic lymphocytes to IL-2, in terms of IL-2-dependent cytotoxic responses, and that this sensitivity is associated with augmented IL-2R beta gene message and cell surface expression.