テラワキ セイゴウ   Seigo Terawaki
  寺脇 正剛
   所属   川崎医科大学  医学部 基礎医学 分子遺伝医学
   職種   特任講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 PD-1-mediated suppression of IL-2 production induces CD8+ T cell anergy in vivo.
掲載誌名 正式名:Journal of immunology (Baltimore, Md. : 1950)
略  称:J Immunol
ISSNコード:15506606/00221767
掲載区分国外
巻・号・頁 182(11),6682-6689頁
著者・共著者 Chikuma Shunsuke, Terawaki Seigo, Hayashi Tamon, Nabeshima Ryusuke, Yoshida Takao, Shibayama Shiro, Okazaki Taku, Honjo Tasuku
発行年月 2009/06
概要 Accumulating evidence suggests that PD-1, an immuno-inhibitory receptor expressed on activated T cells, regulates peripheral T cell tolerance. In particular, PD-1 is involved in the induction and/or maintenance of T cells' intrinsic unresponsiveness to previously encountered Ags, although the mechanism is yet to be determined. We used a simple experimental model to dissect the mechanism for anergy establishment, in which 2C TCR transgenic rag2(-/-) PD-1(+/+) mice were anergized by a single injection of a cognate peptide. Interestingly, 2C rag2(-/-) PD-1(-/-) mice were totally resistant to anergy induction by the same treatment; thus, PD-1 was responsible for anergy induction. Furthermore, PD-1 expression was induced within 24 h of the initial Ag exposure. The establishment of anergy was associated with a marked down-regulation of IL-2 from the CD8(+) T cells. In fact, IL-2 blockade resulted in anergy even in 2C rag2(-/-)PD-1(-/-) T cells. Furthermore, the complementation of the IL-2 signal in 2C rag2(-/-) PD-1(+/+) mice reversed the anergy induction. We propose that CD8(+) T cell anergy is induced by a reduction of cell-autonomous IL-2 synthesis, which is caused by the quick expression of PD-1 in response to Ag stimulation and the subsequent stimulation of this receptor by its ligands on surrounding cells.
DOI 10.4049/jimmunol.0900080
PMID 19454662