TOXは,慢性ウイルス感染症における枯渇したT細胞のフェノタイプと長寿を補強する
Francesca Alfei1, Kristiyan Kanev1, Maike Hofmann2
1Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
Nature
|June 18, 2019
まとめ
ティモサイト選択に関連した高移動性グループボックス (TOX) タンパク質は,慢性感染症の際にT細胞の枯渇に不可欠です. TOXはT細胞の機能不全を維持し,免疫療法とウイルスや腫瘍に対する保護免疫に影響を与えます.
科学分野:
- 免疫学
- 分子生物学
- 細胞生物学
背景:
- 細胞毒性T細胞は感染症や癌と戦うために不可欠ですが,長時間抗原にさらされると枯渇する可能性があります.
- T細胞の疲労は表遺伝的変化,エフェクター機能の低下,PD-1のような抑制受容体の増加を含む.
- T細胞枯渇の分子要因は,まだ完全に理解されていません.
研究 の 目的:
- T細胞枯渇の発生と維持におけるTOXタンパク質の役割を調査する.
- TOXがT細胞の機能障害に影響する 分子機構を理解する
主な方法:
- 慢性ウイルス感染症 (LCMV) のマウスモデルで研究されたT細胞枯渇.
- ヒトのC型肝炎ウイルスの発現を分析した.
- DNA結合ドメインの削除を含む TOXの機能を評価するために 遺伝子操作を利用した.
主要な成果:
- TOXタンパク質は,マウスの枯渇したT細胞の発達と持続に不可欠です.
- TOX発現は,慢性的なLCMV感染とヒトHCVにおけるT細胞枯渇と相関する.
- TOXのDNA結合ドメインの削除により,PD-1の発現が減り,サイトカインの産生が増加し,多機能のT細胞フェノタイプが生じました.
- TOXの消去は最初はエフェクター機能を増加させましたが,最終的にはT細胞,特に自己再生するTCF-1+細胞の数の有意な減少を引き起こしました.
結論:
- TOXはT細胞の機能障害と慢性感染症中のT細胞の維持の重要なレギュラーです.
- TOXは,固有のCD8T細胞エフェクタ機能抑制と免疫病理に対する保護を関連付けています.
- TOXをターゲットにすることで,免疫療法や感染症におけるT細胞の反応を調節する新しい戦略が提供される可能性があります.
関連する概念動画
Viral Recombination
25.0K
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
25.0K
Reinforcement
872
Positive and negative reinforcement are key concepts in operant conditioning, a learning process where the consequences of a behavior affect the likelihood of that behavior being repeated.
Positive reinforcement occurs when a behavior is followed by the presentation of a rewarding stimulus, increasing the frequency of that behavior. For example:
Positive reinforcement occurs when a behavior is followed by the presentation of a rewarding stimulus, increasing the frequency of that behavior. For example:
872
Corrosion of Reinforcement
531
The corrosion of steel reinforcement within concrete is a process influenced by the material's inherent properties and external factors. The high pH level of around 13, provided by calcium hydroxide present in concrete, initially protects the steel reinforcement by promoting the formation of a passive iron oxide layer on its surface.
However, over time and under certain conditions like carbonation, chloride ingress, and cracking this protective state can be compromised. Steel has areas with...
However, over time and under certain conditions like carbonation, chloride ingress, and cracking this protective state can be compromised. Steel has areas with...
531
Reinforcement Schedules
479
Positive reinforcement is a powerful method for teaching new behaviors to both animals and humans. B.F. Skinner demonstrated this with his experiments using rats in a Skinner box. When a rat pressed a lever, it received a food pellet. This immediate reward encouraged the rat to repeat the behavior. This method, where a reward follows every instance of the behavior, is known as continuous reinforcement. It is highly effective for establishing new behaviors quickly.
Once a behavior is learned,...
Once a behavior is learned,...
479
Reinforcements in Concrete
453
Reinforced concrete is a composite material used extensively in construction, combining the compressive strength of concrete with the tensile strength of steel. This synergy is essential as concrete, while excellent at resisting compression, is weak under tension. Steel bars, or rebars, are embedded in the concrete to handle these tensile forces. The choice of steel is strategic; it shares a similar coefficient of thermal expansion with concrete, which ensures uniformity in response to...
453
Viral Structure
74.1K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
74.1K


