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 (C2 GnT1 or C2GlcNAcT1) is responsible for formation of branched structures on O-glyeans present on cell surface glycoproteins. The O-glycan branch create d 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 CD4 3 and CD45RB we have found that in activated CD8(+) T cells expression of C 2GnT1 was dependent upon exposure to specific cytokines rather than being i nduced as a direct consequence of activation. Activated CD8(+) cells became receptive to strong induction of C2GnT1 expression and P-selectin ligand e xpression in response to IL-2, moderate induction by IL-15, and minimal ind uction in response to IL-4. Our observations clarify the relationship betwe en T cell activation and C2GnT1 expression, demonstrate the differential im pact of distinct cytokines on expression of C2GnT1 activity and P-selectin ligand, and reinforce the concept that the cytokine milieu subsequent to ac tivation can influence adhesion systems that dictate lymphocyte homing prop erties.