Effects of polyunsaturated fatty acids on interleukin-2-dependent T cell growth

Abstract

Cellular membranes, in addition to serving as structural constituents of cells, also provide precursors for a number of chemical messengers involved in intracellular signal transduction. This includes the eicosanoids (prostaglandins and leukotrienes) and diacylglycerol, and activator of protein kinase C (PKC). Changes induced in the fatty acid profile of lymphocytes can influence vital metabolic processes in cells. Such changes, independent of the function of fatty acids as prostaglandin and leukotriene precursors, can alter the development and regulation of immune responses. In this report we study the effects of the polyunsaturated fatty acids (PUFA) on proliferation and signal transduction in the interleukin-2 (IL-2)-dependent murine T cell line CTL.L-2. Culture of CTL.L-2 cells in the presence of specific PUFA resulted in their incorporation into the cellular phospholipids. IL-2-induced proliferation of CTL.L-2 cells was markedly suppressed in a dose-dependent fashion by incubation in media supplemented with dihomogammalinolenic acid (an n-6 PUFA) slightly inhibited proliferation, while eicosapentaenoic acid (an n-3 PUFA) had no effect. Neither indomethacin (a cyclooxygenase inhibitor) nor nordihydroguaiaretic acid (NDGA, a lipoxygenase inhibitor) reversed the effect of DGLA. In contrast, phorbol 12-myristate 13-acetate (a phorbol ester and activator of PKC), blocked, in a dose-dependent manner, the antiproliferative effect of DGLA. This study presents evidence that PUFA alter signal transduction in cells in a manner which is separate from their function as eicosanoid precursors. The botanical lipid-derived DGLA has a potent suppressive effect on IL-2-driven T cell proliferation and may alter signal transduction by modification of second messenger or PKC activity.