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 |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | IFN-α directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. |
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 | 186(5),pp.2772-2279 |
著者・共著者 | Terawaki Seigo, Chikuma Shunsuke, Shibayama Shiro, Hayashi Tamon, Yoshida Takao, Okazaki Taku, Honjo Tasuku |
担当区分 | 筆頭著者 |
発行年月 | 2011/03 |
概要 | Programmed cell death-1 (PD-1) is an inhibitory coreceptor for T lymphocytes that provides feedback inhibition of T cell activation. Although PD-1's expression on T cells is known to be activation dependent, the factors that determine the timing, intensity, and duration of PD-1 expression in immune reactions are not fully understood. To address this question, we performed a fine mapping analysis of a conserved 5'-flanking region of the PD-1 gene and identified a putative IFN stimulation response element, which was responsible for PD-1 transcription in the 2B4.11 T cell line. Consistent with this finding, activation by IFN-α enhanced both the induction and maintenance of PD-1 expression on TCR-engaged primary mouse T cells through an association IFN-responsive factor 9 (IRF9) to the IFN stimulation response element. Furthermore, PD-1 expression on Ag-specific CD8(+) T cells was augmented by IFN-α in vivo. We propose that strong innate inflammatory responses promote primary T cell activation and their differentiation into effector cells, but also cause an attenuated T cell response in sustained immune reactions, at least partially through type I IFN-mediated PD-1 transcription. Based on this idea, we demonstrate that IFN-α administration in combination with PD-1 blockade in tumor-bearing mice effectively augments the antitumor immunity, and we propose this as a novel and rational approach for cancer immunotherapy. |
DOI | 10.4049/jimmunol.1003208 |
PMID | 21263073 |