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Lymphocyte Activation in Health and Disease.
Critical Reviews in Immunology ( IF 1.3 ) Pub Date : 2017-01-01 , DOI: 10.1615/critrevimmunol.v37.i2-6.120
Michael J Berridge 1
Affiliation  

Lymphocytes employ a complex assembly of signaling elements that have been organized on a spatiotemporal map to define their role in stimulating both proliferation and apoptosis. The antigen/major histocompatibility complex (MHC) initiates the sequence by organizing the assembly of an active T-cell receptor (TCR) complex responsible for transmitting information down various signaling cassettes (e.g., the IP3/Ca2+, DAG/ PKC, ras/MAPK, and the PI 3-K pathways). It is proposed that CD28 may exert its costimulatory action by facilitating the assembly of an effective scaffold of signaling elements within the TCR complex. The absence of costimulation through CD28 seems to result in the assembly of a defective scaffold that reverses slowly and may thus account for the state of unresponsiveness responsible for peripheral T-cell tolerance. The signaling cassettes activated by the TCR and CD28 then engage cytosolic factors that transmit information into the nucleus to activate the genes that code for the IL-2 and Fas signaling pathways. The IL-2 and Fas receptors employ additional signaling cassettes (e.g., the JAK/STAT and the sphingomyelinase/ceramide pathways) to mediate their effects on proliferation and apoptosis, respectively. Information concerning these signaling systems is beginning to provide therapeutic strategies to manipulate the immune system to overcome human immunodeficiency virus (HIV) infection, autoimmune diseases, and graft rejection.

中文翻译:

健康与疾病中的淋巴细胞活化。

淋巴细胞采用复杂的信号传导元件组装,这些信号传导元件已在时空图上进行组织,以定义其在刺激增殖和凋亡中的作用。抗原/主要组织相容性复合物(MHC)通过组织负责在各种信号传递盒(例如IP3 / Ca2 +,DAG / PKC,ras / MAPK)下传递信息的活性T细胞受体(TCR)复合物的装配来启动序列,以及PI 3-K途径)。提出CD28可以通过促进TCR复合物中的信号传导元件的有效支架的组装来发挥其共刺激作用。通过CD28缺乏共刺激似乎导致组装了一个有缺陷的支架,该支架缓慢反转,因此可以解释造成外周T细胞耐受性的无反应状态。然后,由TCR和CD28激活的信号盒与胞质因子结合,这些因子将信息传递到细胞核中,从而激活编码IL-2和Fas信号通路的基因。IL-2和Fas受体分别采用其他信号传导盒(例如JAK / STAT和鞘磷脂酶/神经酰胺途径)来介导它们对增殖和凋亡的影响。有关这些信号系统的信息正开始提供治疗策略,以操纵免疫系统克服人类免疫缺陷病毒(HIV)感染,自身免疫性疾病和移植排斥。IL-2和Fas受体分别采用其他信号传导盒(例如JAK / STAT和鞘磷脂酶/神经酰胺途径)来介导它们对增殖和凋亡的影响。有关这些信号系统的信息正开始提供治疗策略,以操纵免疫系统克服人类免疫缺陷病毒(HIV)感染,自身免疫性疾病和移植排斥。IL-2和Fas受体分别采用其他信号传导盒(例如JAK / STAT和鞘磷脂酶/神经酰胺途径)来介导它们对增殖和凋亡的影响。有关这些信号系统的信息正开始提供治疗策略,以操纵免疫系统克服人类免疫缺陷病毒(HIV)感染,自身免疫性疾病和移植排斥。
更新日期:2019-11-01
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