Differential expression of alpha3 fucosyltransferases in Th1 and Th2 cells correlates with their ability to bind P-selectin.

One of the key control points in the trafficking of the T cell effector subsets, Th1 and Th2, to sites of inflammation is their migration out of the bloodstream. The mechanism by which the cells initially adhere to the endothelium is dependent on the selectin family of adhesion molecules. Only polarised Th1 cells are capable of binding P-selectin despite both Th1 and Th2 cells expressing PSGL-1, the P-selectin ligand. This may be due to a secondary modification of PSGL-1 that is present on Th1 but not Th2 cells. One key modification of PSGL-1 is the alpha3 fucosylation of the O-glycans. To address whether the binding of Th1 and Th2 cells may be regulated by fucosylation, we have studied the expression of the alpha3 fucosyltransferases, FucT-IV and VII, using in vitro differentiated mouse T cells. Messenger RNA levels for both FucT-IV and VII were found to be higher in Th1 than Th2 cells. alpha3 fucosyltransferase enzyme activities were also elevated in Th1 cells. The increased expression of the alpha3 fucosyltransferases in Th1 cells correlated with the ability of Th1, but not Th2, cells to bind to P-selectin. Thus, the regulation of the binding of effector T cells to the endothelium, and subsequent trafficking to inflammatory sites, may be controlled by the fucosylation state of PSGL-1 mediated by the selective expression of the alpha3 fucosyltransferases.