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),pp.6682-6689
著者・共著者	Chikuma Shunsuke, Terawaki Seigo, Hayashi Tamon, Nabeshima Ryusuke, Yoshida Takao, Shibayama Shiro, Okazaki Taku, Honjo Tasuku
担当区分	2nd著者
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