Seigo Terawaki
Department Kawasaki Medical School Kawasaki Medical School, Department of Molecular and Genetic Medicine, Position Assistant Professor with Special Assignment |
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Article types | 原著 |
Language | English |
Peer review | Peer reviewed |
Title | PD-1-mediated suppression of IL-2 production induces CD8+ T cell anergy in vivo. |
Journal | Formal name:Journal of immunology (Baltimore, Md. : 1950) Abbreviation:J Immunol ISSN code:15506606/00221767 |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 182(11),pp.6682-6689 |
Author and coauthor | Chikuma Shunsuke, Terawaki Seigo, Hayashi Tamon, Nabeshima Ryusuke, Yoshida Takao, Shibayama Shiro, Okazaki Taku, Honjo Tasuku |
Authorship | 2nd author |
Publication date | 2009/06 |
Summary | 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 |