Expression of cutaneous lymphocyte-associated antigen regulated by a set of glycosyltransferases in human T cells: involvement of alpha1, 3-fucosyltransferase VII and beta1,4-galactosyltransferase I.
Cutaneous lymphocyte-associated antigen (CLA), which plays a key part in skin homing of human CD4+ memory T cells via CLA/E-selectin binding, is upregulated by IL-12 and downregulated by IL-4. Although alpha1,3-fucosyltransferase VII is essential for synthesis of the CLA carbohydrate epitope, little is known about how the CLA expression is regulated by a number of glycosyltransferases. A 6 wk long-term culture for the in vitro differentiation of naïve Th cells to memory Th1 cells was employed. By repeated activation in the presence of IL-12, naïve T cells differentiated into memory Th1 cells, resulting in the upregulation of CLA expression. The switching of cytokine from IL-12 to IL-4 at three cycles resulted in a marked downregulation of CLA. The transcript levels of 16 glycosyltransferases and P-selectin glycoprotein ligand-1, all considered to be potentially involved in CLA synthesis, were determined after each cycle. The level of CLA expression was well correlated with the amounts of alpha1,3-fucosyltransferase VII and beta1,4-galactosyltransferase I. Both were upregulated by IL-12 and downregulated by IL-4. In particular, alpha1,3-fucosyltransferase VII levels decreased markedly in the presence of IL-4. P-selectin glycoprotein ligand-1 and Core 2 beta1, 6-N-acetylglucosaminyltransferase were progressively up-regulated by repeated IL-12 stimulation, but they were not downregulated by IL-4. The transcript levels of some genes examined were constitutive without any correlation to CLA expression. These results suggest that the level of CLA expression is determined by alpha1, 3-fucosyltransferase VII and beta1,4-galactosyltransferase I, the other enzymes merely participating in the synthesis of CLA. In peripheral blood mononuclear cells, IL-12 and IL-4 profoundly upregulated and downregulated the alpha1,3-fucosyltransferase VII transcripts, respectively, but not the beta1,4-galactosyltransferase I ones, within only 2 h of in vitro culture. This suggested that alpha1,3-fucosyltransferase VII is transcriptionally regulated directly by IL-12 and IL-4.
Nakayama
F
F
Division of Cell Biology, Institute of Life Science, Soka University, Tokyo, Japan.
Teraki
Y
Y
Kudo
T
T
Togayachi
A
A
Iwasaki
H
H
Tamatani
T
T
Nishihara
S
S
Mizukawa
Y
Y
Shiohara
T
T
Narimatsu
H
H
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D005647:Fucosyltransferases / Q000502:physiology; D016695:Glycosyltransferases / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology*; D018417:Th1 Cells / Q000166:cytology
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D007527:Isoenzymes; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D016695:Glycosyltransferases; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase