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T Cell Activation Pathways: B7, LFA-3, and ICAM-1 Shape Unique T Cell Profiles.
Critical Reviews in Immunology ( IF 0.8 ) Pub Date : 2017-01-01 , DOI: 10.1615/critrevimmunol.v37.i2-6.130
Anette Gjorloff Wingren 1 , Eduardo Parra 1 , Mikael Varga 2 , Terje Kalland 3 , Hans-Olov Sjogren 1 , Gunnar Hedlund 3 , Mikael Dohlsten 3
Affiliation  

Two signals are required for induction of cell proliferation and cytokine production in resting T cells. Occupancy of the T cell receptor by antigen/MHC complexes delivers the first signal to the T cell, while the second signal is provided by interaction with costimulatory ligands on APC. CD2, LFA-1, and CD28 are the major costimulatory and adhesive molecules on T cells and bind to the LFA-3, ICAM-1 and B7 ligands, respectively, on APC. LFA-3 plays a central role for naive and memory T helper cells during the early phase of an immune response. The LFA-3/CD2 pathway initiates strong antigen-independent cell adhesion, substantial expansion of naive T helper cells, and induction of large amounts of IFN-γ in memory cells. The release of IFN-γ may upregulate expression of ICAM-1 and B7 on APC and allows multiple adhesion pathways to amplify the immune response. The LFA- 1/ICAM-l pathway stimulates adhesion and cell proliferation more efficiently in memory T helper cells than in naive cells. Further, the results suggest that naive T helper cells express functionally inactive LFA-1 molecules on the cell surface, which may have a physiological role in keeping these cells in a resting state. B7 costimulation superinduces IL-2 production in both naive and memory T helper cells and generates long-lasting cell proliferation. This permits transition from an autocrine to a paracrine immune response. Coexpression of B7/LFA-3 provides an optimal APC function and enables a vigorous T cell response to minute amounts of antigen. AP-1 and NF-κB transcription factors are involved in the induction of several cytokine gene promoters and play a central role in the regulation of IL-2 gene transcription. LFA-3 costimulation only moderately enhances AP-1 DNA-binding activity and does not influence the NF-κB activity induced by TCR engagement, whereas B7 costimulation induces large amounts of NF-κB and AP-1 activity in T helper cells. The costimulatory ligands represent a family of adhesion molecules with considerable redundancy. Interfamily redundancy of LFA-3, B7, and ICAM ligands offers an opportunity to regulate distinct T cell response profiles in various microenvironments at separate time points of an immune response.

中文翻译:

T细胞活化途径:B7,LFA-3和ICAM-1形成独特的T细胞谱。

在静息T细胞中诱导细胞增殖和细胞因子产生需要两个信号。抗原/ MHC复合体对T细胞受体的占用将第一个信号传递给T细胞,而第二个信号是通过与APC上的共刺激配体相互作用而提供的。CD2,LFA-1和CD28是T细胞上的主要共刺激分子和粘附分子,分别与APC上的LFA-3,ICAM-1和B7配体结合。LFA-3在免疫应答的早期阶段对幼稚和记忆T辅助细胞起着核心作用。LFA-3 / CD2途径可引发强烈的非抗原依赖性细胞粘附,幼稚T辅助细胞的大量扩增以及记忆细胞中大量IFN-γ的诱导。IFN-γ的释放可能会上调APC上ICAM-1和B7的表达,并允许多种粘附途径来增强免疫反应。在记忆T辅助细胞中,LFA-1 / ICAM-1途径比在幼稚细胞中更有效地刺激粘附和细胞增殖。此外,结果表明,幼稚的T辅助细胞在细胞表面表达功能失活的LFA-1分子,这可能在使这些细胞保持静止状态方面具有生理作用。B7共刺激在幼稚和记忆T辅助细胞中都诱导IL-2的产生,并产生持久的细胞增殖。这允许从自分泌转变为旁分泌免疫应答。B7 / LFA-3的共表达可提供最佳的APC功能,并使T细胞对微量的抗原产生强烈的反应。AP-1和NF-κB转录因子参与几种细胞因子基因启动子的诱导,并在IL-2基因转录的调控中发挥重要作用。LFA-3共刺激仅适度增强AP-1 DNA结合活性,并且不影响TCR参与诱导的NF-κB活性,而B7共刺激在T辅助细胞中诱导大量NF-κB和AP-1活性。共刺激配体代表具有大量冗余的粘附分子家族。LFA-3,B7和ICAM配体的家族间冗余提供了一个机会,可以在免疫反应的不同时间点在各种微环境中调节不同的T细胞反应谱。LFA-3共刺激仅适度增强AP-1 DNA结合活性,并且不影响TCR参与诱导的NF-κB活性,而B7共刺激在T辅助细胞中诱导大量NF-κB和AP-1活性。共刺激配体代表具有大量冗余的粘附分子家族。LFA-3,B7和ICAM配体的家族间冗余提供了一个机会,可以在免疫反应的不同时间点在各种微环境中调节不同的T细胞反应谱。LFA-3共刺激仅适度增强AP-1 DNA结合活性,并且不影响TCR参与诱导的NF-κB活性,而B7共刺激在T辅助细胞中诱导大量NF-κB和AP-1活性。共刺激配体代表具有大量冗余的粘附分子家族。LFA-3,B7和ICAM配体的家族间冗余性提供了一个机会,可以在免疫反应的不同时间点在各种微环境中调节不同的T细胞反应谱。
更新日期:2019-11-01
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