Alpha(1,3)-fucosyltransferase VII and alpha(2,3)-sialyltransferase IV are up-regulated in activated CD4 T cells and maintained after their differentiation into Th1 and migration into inflammatory sites.
Activated Th1 CD4 T cells bind to P-selectin and migrate into inflamed tissue, whereas Th2 cells do not. We show that alpha(1, 3)-fucosyltransferase VII (FucT-VII) and alpha(2, 3)-sialyltransferase IV (ST3GalIV), which are crucial for the biosynthesis of functional P-selectin ligands, are absent in naive CD4 T cells, but are rapidly up-regulated upon activation. Th1 or Th2 differentiation in the presence of polarizing cytokines leads to down-regulation of FucT-VII mRNA selectively in Th2 but not in Th1 cells. Influencing the differentiation by varying the priming dose of antigenic peptide results in similar FucT-VII down-regulation only in Ag-specific Th2 cells. ST3GalIV levels remain elevated. FucT-VII and ST3GalIV mRNAs are also up-regulated by Th1 cells primed in vivo and recruited into the lymph nodes draining delayed-type hypersensitivity sites. We identify FucT-VII gene expression as a principal difference between Th1 and Th2 cells, and underscore the importance of FucT-VII and ST3GalIV expression for the biosynthesis of functional selectin ligands.
Blander
J M
JM
Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06520, USA.
Visintin
I
I
Janeway
C A
CA
Medzhitov
R
R
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis; D005647:Fucosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D005732:Gangliosides / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007399:Interphase / Q000276:immunology; D007983:Lewis Blood Group Antigens / Q000276:immunology; D008198:Lymph Nodes / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases / Q000096:biosynthesis*; D018417:Th1 Cells / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D018984:Epitopes, T-Lymphocyte; D005732:Gangliosides; D000949:Histocompatibility Antigens Class II; D007983:Lewis Blood Group Antigens; D010446:Peptide Fragments; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; C094688:sialyl Lewis(x) ganglioside; D018664:Interleukin-12; D015847:Interleukin-4; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase