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著作: Mizuno Reina/[杉浦 大祐]/Shimizu Kenji/[丸橋 拓海]/Watada Mizuki/[岡崎 一美]/[岡崎 拓]/PD-1 Primarily Targets TCR Signal in the Inhibition of Functional T Cell Activation./[Frontiers in Immunology]

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EID
356649
EOID
956583
Map
0
LastModified
2019年8月19日(月) 11:34:32
Operator
岡崎 拓
Avail
TRUE
Censor
0
Owner
岡崎 拓
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨
共著種別 推奨
学究種別 推奨
組織 推奨
著者 必須
  1. (英) Mizuno Reina
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. 杉浦 大祐
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Shimizu Kenji
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. 丸橋 拓海
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. (英) Watada Mizuki
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. 岡崎 一美
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. 岡崎 拓
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) PD-1 Primarily Targets TCR Signal in the Inhibition of Functional T Cell Activation.

副題 任意
要約 任意

(英) Cancer-immunotherapy targeting programmed cell death 1 (PD-1) activates tumor-specific T cells and provides clinical benefits in various cancers. However, the molecular basis of PD-1 function is still enigmatic. Especially, it is unclear which signaling pathway PD-1 primarily targets. Besides, the capacity of PD-1 to inhibit the T cell receptor (TCR)-dependent activation of T cells in the presence of co-stimulation is also controversial. Here we used co-culture systems of T cells and antigen-presenting cells with targeted deletion and overexpression of co-receptors and ligands and examined the inhibitory potency of PD-1 against T cell activation upon TCR stimulation with CD28 and ICOS co-stimulation. As an unambiguous criterion of T cell activation, we used the acquisition of cytokine production capacity, which represents one of the most important functions of T cells. PD-1 inhibited functional T cell activation upon TCR stimulation in the absence as well as in the presence of CD28 co-stimulation, indicating that PD-1 can directly inhibit TCR signal. Notably, CD28 co-stimulation rather attenuated the efficiency of PD-1 in inhibiting TCR-dependent functional T cell activation. In addition, PD-1 inhibited TCR-dependent functional T cell activation with ICOS co-stimulation as efficiently as that with CD28 co-stimulation. Furthermore, we found that the maintenance of antigen-induced follicular helper T (T) cells that required ICOS co-stimulation was persistently restrained by PD-1 . These findings indicate that PD-1 primarily targets TCR signal in the inhibition of functional T cell activation. Thus, PD-1 functions as the rheostat of T cell activation rather than an inhibitor of a specific stimulatory co-receptor.

キーワード 推奨
発行所 推奨
誌名 必須 Frontiers in Immunology(Frontiers Research Foundation)
(eISSN: 1664-3224)
ISSN 任意 1664-3224
ISSN: 1664-3224 (eISSN: 1664-3224)
Title: Frontiers in immunology
Title(ISO): Front Immunol
Publisher: Frontiers Media S.A.
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 10
必須
必須 630 630
都市 任意
年月日 必須 2019年 3月 29日
URL 任意
DOI 任意 10.3389/fimmu.2019.00630    (→Scopusで検索)
PMID 任意 31001256    (→Scopusで検索)
NAID 任意
WOS 任意
Scopus 任意
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.ELocationID: 10.3389/fimmu.2019.00630

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) KeywordList.Keyword: CD28

  4. (英) KeywordList.Keyword: ICOS

  5. (英) KeywordList.Keyword: PD-1

  6. (英) KeywordList.Keyword: T cell receptor

  7. (英) KeywordList.Keyword: co-receptor

  8. (英) KeywordList.Keyword: cytokine production

  9. (英) KeywordList.Keyword: follicular helper T cell