Seigo Terawaki
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Molecular and Genetic Medicine,
   Position   Assistant Professor with Special Assignment
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 / ForeginForegin
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