Analysis of mechanisms by which CD8^+ T cells differentiate into the skin-homing phenotype

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In this study, we asked how expression of two fucosyltransferases (Fuc Ts), Fuc T-IV and Fuc T-VII, can be regulated in the process of skin-homing CD8^+ T cell differentiation. We demonstrated with the use of transfectants that E-selectin ligand (ESL) epitope generated by Fuc T-IV is different from that generated by Fuc T-VII ; and that Fuc T-IV generates only low. levels of ESL without CLA expression while Fuc T-VII constructs high levels of ESL with concomitant expression of CLA. Our phenotypic analysis of memory CD8^+ T cells differentiated from naive T cells under various conditions showed that the transition from the ESL^+CLA^- to the ESL^<++>CLA^+ phenotype progressively occurred in parallel with down-regulation of Fuc T-IV expression when transferred to resting culture with IL-12. In contrast, Fuc T-VII expression was down-regulated as the T cells were transferred to IL-4-rich resting culture, where Fuc T-IV remained unchanged and the ESL^<++>CLA^+ phenotype was not detected. These results indicate that under conditions where Fuc T-IV is abundantly expressed the Fuc T-VII-dependent ESL is prevented from cell surface expression ; however, once availability of the substrate, N-acetyllactosamine, is limited, Fuc T-IV is down-regulated due to competition of this substrate, thereby allowing the T cell to express the Fuc T-VII-dependent ESL epitope with high avidity to E-selectin. Thus, the dynamic balance between Fuc T-IV and Fuc T-VII depending on their state of a activation and differentiation is a major check point for the regulation of skin-homing CD8^+ T cell differentiation.