Expression of cutaneous lymphocyte-associated antigen regulated by a set of glycosyltransferases in human T cells: Involvement of alpha 1,3-fucosyltransferase VII and beta 1,4-galactosyltransferase I

Cutaneous lymphocyte-associated antigen (CLA), which plays a key part in sk in homing of human CD4(+) memory T cells via CLA/E-selectin binding, is upr egulated by IL-12 and downregulated by IL-4. Although alpha 1,3-fucosyltran sferase VII is essential for synthesis of the CLA carbohydrate epitope, lit tle is known about how the CLA expression is regulated by a number of glyco syltransferases. A 6 wk long-term culture for the in vitro differentiation of naive Th cells to memory Th1 cells was employed. By repeated activation in the presence of IL-12, naive T cells differentiated into memory Th1 cell s, resulting in the upregulation of CLA expression. The switching of cytoki ne from IL-12 to IL-4 at three cycles resulted in a marked downregulation o f CLA. The transcript levels of 16 glycosyltransferases and P-selectin glyc oprotein ligand-1, all considered to be potentially involved in CLA synthes is, were determined after each cycle. The level of CLA expression was well correlated with the amounts of alpha 1,3-fucosyltransferase VII and beta 1, 4-galactosyltransferase I. Both were upregulated by IL-12 and downregulated by IL-4. In particular, alpha 1,3-fucosyltransferase VII levels decreased markedly in the presence of IL-4. P-selectin glycoprotein ligand-1 and Core 2 beta 1,6-N-acetylglucosaminyltransferase were progressively up-regulated by repeated IL-12 stimulation, but they were not downregulated by IL-4. Th e transcript levels of some genes examined were constitutive without any co rrelation to CLA expression. These results suggest that the level of CLA ex pression is determined by alpha 1,3-fucosyltransferase VII and beta 1,4-gal actosyltransferase I, the other enzymes merely participating in the synthes is of CLA. In peripheral blood mononuclear cells, IL-12 and IL-4 profoundly upregulated and downregulated the alpha 1,3-fucosyltransferase VII transcr ipts, respectively, but not the beta 1,4-galactosyltransferase I ones, with in only 2 h of in vitro culture. This suggested that alpha 1,3-fucosyltrans ferase VII is transcriptionally regulated directly by IL-12 and IL-4.