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Interleukin 12 and Interleukin 4 Control T Cell Adhesion to Endothelial Selectins through Opposite Effects on 1,3-fucosyltransferase VII Gene Expression

Amy J. Wagers^*, Christopher M. Waters, Lloyd M. Stoolman, and Geoffrey S. Kansas^*

From the ^* Department of Microbiology-Immunology and the Departments of Biomedical Engineering and Anesthesiology, Northwestern Medical School, Chicago, Illinois 60611; and the Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109

The 1,3-fucosyltransferase, FucT-VII, is crucial for the formation of ligands for all three selectins, and its expression regulates the synthesis of these ligands. Short-term polarized T helper (Th)1, but not Th2 or naive CD4⁺ T cells, can home to sites of inflammation, but the molecular basis for this difference has remained unclear. Here we show that naive CD4⁺ T cells do not express FucT-VII and fail to bind vascular selectins. We also 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 binding to E- and P-selectin are significantly augmented. In contrast, activation of CD4⁺ T cells in the presence of IL-4, a Th2 polarizing cytokine, inhibited FucT-VII expression and binding to vascular selectins. T cell activation upregulated expression of the Core2 transferase, C2GnT, equivalently regardless of the presence or absence of polarizing cytokines. These data indicate 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.

Key Words: selectin • T helper cell type 1 and T helper cell type 2 • fucosyltransferase • cytokine • gene expression

G.S. Kansas is an Established Investigator of the American Heart Association; A.J. Wagers is a predoctoral fellow of the National Science Foundation. This study was supported by grants from the American Cancer Society and the National Institutes of Health.

¹ Abbreviations used in this paper: C2GnT, core 2 β1,6-N-acetylglucosaminyltransferase; CHO, Chinese hamster ovary; CLA, HECA-452 antigen; CM, complete media; FucT-VII, 1,3-fucosyltransferase VII; PGK1, phosphoglycerate kinase 1; RIgM, selectin-IgM; TSST-1, toxic shock syndrome toxin-1.

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