IL-2, -4, and -15 differentially regulate O-glycan branching and P-selectin ligand formation in activated CD8 T cells.
The glycosyltransferase core 2 beta1-6 N-acetylglucosaminyl transferase (C2GnT1 or C2GlcNAcT1) is responsible for formation of branched structures on O-glycans present on cell surface glycoproteins. The O-glycan branch created by C2GnT1 is physiologically important insofar as only this structure can be extended and modified to yield P-selectin ligands that promote initial interactions between extravasating lymphocytes and endothelia. In mature T cells, C2GnT1 activity is thought to be induced as an intrinsic consequence of T cell activation. Through analysis of C2GnT1-dependent epitopes on CD43 and CD45RB we have found that in activated CD8(+) T cells expression of C2GnT1 was dependent upon exposure to specific cytokines rather than being induced as a direct consequence of activation. Activated CD8(+) cells became receptive to strong induction of C2GnT1 expression and P-selectin ligand expression in response to IL-2, moderate induction by IL-15, and minimal induction in response to IL-4. Our observations clarify the relationship between T cell activation and C2GnT1 expression, demonstrate the differential impact of distinct cytokines on expression of C2GnT1 activity and P-selectin ligand, and reinforce the concept that the cytokine milieu subsequent to activation can influence adhesion systems that dictate lymphocyte homing properties.
Carlow
D A
DA
Biomedical Research Centre and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. doug@brc.ubc.ca
Corbel
S Y
SY
Williams
M J
MJ
Ziltener
H J
HJ
D000818:Animals; D015703:Antigens, CD; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051917:Leukosialin; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000235:genetics; D019007:P-Selectin / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D019409:Interleukin-15; D007376:Interleukin-2; D051917:Leukosialin; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; D011134:Polysaccharides; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D015847:Interleukin-4; D017351:N-Acetylglucosaminyltransferases; D017493:Leukocyte Common Antigens