RRR-alpha-tocopheryl succinate inhibition of lectin-induced T cell proliferation

The effect of RRR-alpha-tocopheryl succinate (VES) on lectin-induced chicken T cell proliferation was investigated. The T cell mitogens concanavalin A and phytohemagglutinin induce chicken thymic and splenic T cell proliferation. Addition of VES to the in vitro cultures inhibited T cell proliferation in a dose-dependent manner. Addition of VES to spleen cell cultures at different times after mitogen stimulation also suppressed T cell mitogenesis, suggesting that VES is not mediating its antiproliferative effects by interfering with ligand (mitogen)-receptor binding or early ligand-bound receptor-signaling events. Three lines of evidence suggest that the growth-inhibitory properties of VES are unique and may not involve antioxidant properties. 1) Three other forms of vitamin E, dl-alpha-tocopherol, d-alpha-tocopherol, and d-alpha-tocopherol acetate, do not inhibit the proliferation of mitogen-stimulated chicken spleen cells. 2) Spleen cells were treated with an inhibitor of nonspecific esterases to prevent the conversion of VES, which does not exhibit antioxidant properties to d-alpha-tocopherol, a lipid-soluble antioxidant. Treatment of spleen cells with the inhibitor did not affect VES's growth-inhibitory properties. 3) Trolox, a water-soluble vitamin E analogue with potent antioxidant properties and two lipid-soluble antioxidants, butylated hydroxyanisole and butylated hydroxytoluene, did not inhibit mitogen-induced T cell proliferation. Attempts to reverse VES's antiproliferative effects by addition of exogenous interleukin-2 or addition of sodium selenite, an enhancer of interleukin-2 receptors, failed. Acetylsalicylic acid had no effect on VES's inhibition of mitogen-activated T cell proliferation. These studies support the role of VES as a growth inhibitor of lectin-activated normal T cells in chickens.