皮膚科学教室 塩原哲夫教授（共研FCM部門部門長）の指導のもとに、重症薬疹である薬剤性過敏性症候群(Drug-induced hypersensitivity syndrome;DIHS)及びスティーブンス・ジョンソン症候群(Stevens Johnson Syndrome;SJS)・中毒性表皮壊死症(Toxic Epidermal Necrolysis;TEN)の病態発生機序に関する研究を進めてまいりましたが、これらの重症薬疹の発生機序に制御性T細胞（Regulatory T Cell; Treg）が深く関与しているという研究結果を、免疫学雑誌『The Journal of Immunology』に発表しました。
The Journal of Immunology, 2009, 182: 8071-8079.
Defective Regulatory T Cells In Patients with Severe Drug Eruptions: Timing of the Dysfunction Is Associated with the Pathological Phenotype and Outcome
Ryo Takahashi,1, Yoko Kano,2, Yoshimi Yamazaki,2, Momoko Kimishima,2, Yoshiko Mizukawa,2, and Tetsuo Shiohara,1,2,
1 Division of Flow Cytometry, Kyorin University Graduate School of Medicine and 2 Department of Dermatology, Kyorin University School of Medicine, Shinkawa, Mitaka, Tokyo, JapanToxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS) represent two ends of a spectrum of severe drug eruptions: DIHS is unique in that severe epidermal damage seen in TEN is absent, sequential reactivations of herpesviruses occur, and autoimmunity often ensues. To investigate whether changes in regulatory T (Treg) cell function would contribute to variability in the clinical manifestations, we examined the frequency, phenotype, and function of Treg cells both during the acute stage and again long after clinical resolution of both diseases. Dramatic expansions of functional Treg cells were found in the acute stage of DIHS. In contrast, Treg function was profoundly impaired in TEN, although present in normal frequency. Skin homing addressins were more preferentially expressed on Treg cells in DIHS than in TEN. Indeed, Treg cells were more abundantly present in the skin lesions of DIHS. Surprisingly, Treg cells contracted upon resolution of DIHS became functionally deficient, whereas their functional defects in TEN were restored upon recovery. These findings indicate that a transitory impairment in their function during the acute stage of TEN may be related to severe epidermal damage, while a gradual loss of their function after resolution of DIHS may increase the risk of subsequently developing autoimmune disease.