| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Current models generally assume that the increase in circulating CLA^+ T cells observed in atopic dermatitis (AD) patients represents the expansion of skin-homing T cells responsible for local inflammation and tissue damage. However, the increase can be easily explained by altered T cell trafficking. By using a novel mAb for fucosyltransferase VII (Fuc-TVII), we previously established double staining procedures that can accurately identify subpopulations of skin-homing T cells : Fuc-TVII^+ CLA^+, Fuc-TVII^+ CLA^+, and Fuc-TVII^-CLA^+. In this study, we asked which subpopulations were increased in AD patients and whether this increase could have significant implications for immunopathology in the inflammatory sites. In the purified CD4^+ T cells of healthy controls, only about 4% expressed both CLA and Fuc-TVII : this subpopulation was shown to be most avidily bound to E-selectin. The most abundantly identifiable phenotype was Fuc-TVII^-CLA^+ (6%), most of which lost their ability to bind E-selectin. In AD patients, the Fuc-TVII^+ CLA^+ was dramatically increased about three-fold in the frequency (11%) as compared with controls. Next, we asked whether the increased subset could be associated with the generation of ESL (E-selectin ligand) and which chemokine receptors were preferentially expressed on this subset. Surprisingly, while the frequencies of ESL^+CLA^+ Th cells in controls ranged from 4 to 7%, those in AD dramatically increased up to 14%, correlating with the increased frequencies of the Fuc-TVII^+CLA^+ subset The vast majority of this subset was of Th 2 phenotype, because they expressed CCR-4 but not CXCR-3. These results indicate that in AD Th 2 cells accumulate in the circulation despite their ability to migrate into the skin. AD may be a disease of abnormal T cell trafficking in which Th 2 cells fail to traffic efficiently to the skin
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