2004 Fiscal Year Final Research Report Summary
Analysis of mechanisms by which CD8^+ T cells differentiate into the skin-homing phenotype
| Project/Area Number |
15390344
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kyorin University |
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Principal Investigator |
SHIOHARA Tetsuo Kyorin University, School of Medicine, Department of Dermatology, Professor, 医学部, 教授 (10118953)
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| Co-Investigator(Kenkyū-buntansha) |
TERAKI Yuichi Kyorin University, School of Medicine, Department of Dermatology, Assistant Professor, 医学部, 講師 (10188667)
MIZUKAWA Yoshiko Kyorin University, School of Medicine, Department of Dermatology, Instructor, 医学部, 助手 (50301479)
HAYAKAWA Jun Kyorin University, School of Medicine, Department of Dermatology, Instructor, 医学部, 助手 (30255393)
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| Project Period (FY) |
2003 – 2004
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| Keywords | skin-homing / CD8^+ T cell / E-selectin ligand / fucosyltransferase / CLA / CCR-4 / cytokine |
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| Research Abstract |
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.
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