Interleukin 12 and interleukin 4 control cell adhesion to endothelial selectins through opposite effects on alpha 1,3-fucosyltransferase VII gene expression

The alpha 1,3-fucosyltransferase, FucT-VII, is crucial for the formation of ligands for all three selectins, and its expression regulates the synthesi s of these ligands. Short-term polarized T helper (Th)1, but not Th2 or nai ve CD4(+) T cells, can home to sites of inflammation, but the molecular bas is for tills difference has remained unclear. Here we show that naive CD4() T cells do not express FucT-VII and fail to bind vascular selectins. We a lso show that when CD4(+) T cells are activated in the presence of the Th1 polarizing cytokine interleukin (IL)-12, levels of FucT-VII mRNA and bindin g to E- and P-selectin are significantly augmented. In contrast, activation of CD4(+) T tells ill the presence of IL-4, a Th2 polarizing cytokine, inh ibited FucT-VII expression and binding to vascular selectins. T cell activa tion upregulated expression of the Core2, transferase, C2GnT, equivalently regardless of the presence or absence of polarizing cytokines. These data i ndicate that the selective ability of Th1 cells, as opposed to Th2 cells or naive CD4(+) T cells, to recognize vascular selectins and home to sites of inflammation is controlled principally by the expression of a single gene, FucT-VII.