Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; leukotriene B₄ induces an OKT8(+), radiosensitive suppressor cell from resting, human OKT8(-) T cells

We report that leukotriene B₄ (LTB₄), a 5-lipoxygenase metabolite of arachidonic acid, is a potent suppressor of polyclonal Ig production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood lymphocytes, while LTC₄ and LTD₄ have little activity in this system. Preincubation of T cells with LTB₄ in nanomolar to picomolar concentrations rendered these cells suppressive of Ig production in subsequent PWM-stimulated cultures of fresh, autologous B + T cells. This LTB₄-induced suppressor cell was radiosensitive, and its generation could be blocked by cyclohexamide but not by mitomycin C. The LTB₄-induced suppressor cell was OKT8(+), while the precursor for the cell could be OKT8(-). The incubation of OKT8(-) T cells with LTB₄ for 18 h resulted in the appearance of the OKT8(+) on 10-20% of the cells, and this could be blocked by cyclohexamide but not by mitomycin C. Thus, LTB₄ in very low concentrations induces a radiosensitive OKT8(+) suppressor cell from OKT8(-) cells. In this regard, LTB₄ is three to six orders of magnitude more potent than any endogenous hormonal inducer of suppressor cells previously described. Glucocorticosteroids which block suppressor cell induction in many systems, may act by inhibiting endogenous production of LTB₄.