Enhanced expression of CTLA‐4 (CD152) on CD4+ T cells in HIV infection

Enhanced expression of CTLA‐4 (CD152) on CD4+ T cells in HIV infection
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HIV 感染中 CD4+ T 细胞上 CTLA-4 (CD152) 的表达增强

DOI:
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发表时间:
1999
影响因子:
4.6
通讯作者:
Bröker
Bröker
中科院分区:
医学3区
文献类型:
--
作者:
Steiner;Waase;Raú;Dietrich;Fleischer;Bröker

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CTLA-4(CD 152)是活化T细胞的表面分子,与CD 28具有序列同源性。两种分子结合相同的配体B7.1(CD 80)和B7.2(CD 86),但具有拮抗功能。虽然CD 28是一种重要的共刺激分子,但CTLA-4在维持免疫系统的稳态方面具有重要的抑制功能。在HIV感染中已经描述了主要在CD 8 + T细胞上的CD 28的下调,但是CTLA-4的分析由于其低表达水平而变得复杂。在这里,我们使用有效的信号增强来研究HIV感染期间外周血单核细胞(PBMC)上的CTLA-4。CTLA-4仅在T细胞上表达。在HIV感染的所有阶段,CD 4 + T细胞上的表达水平选择性地显著增加,而CD 8 + T细胞上的CTLA-4表达总是很低。相比之下,在用促分裂原植物血凝素(PHA)刺激后,CTLA-4水平在对照组的T细胞上强烈增加,但在HIV患者的T细胞中,这种反应严重受损。我们的数据表明,在HIV感染中,CD 4+和CD 8 + T细胞可能对B7共刺激的反应性较低,这是由于两种不同的机制:CD 4+细胞表达CTLA-4增加和CD 8+细胞下调CD 28。
CTLA‐4 (CD152) is a surface molecule of activated T cells with sequence homology to CD28. Both molecules bind to the same ligands, B7.1 (CD80) and B7.2 (CD86) but have antagonistic functions. While CD28 is an important costimulator, CTLA‐4 has an essential inhibitory function in maintaining the homeostasis of the immune system. Down‐ regulation of CD28 predominantly on CD8+ T cells has been described in HIV infection, but analysis of CTLA‐4 is complicated by its low expression levels. Here we have used potent signal enhancement to study CTLA‐4 on peripheral blood mononuclear cells (PBMC) during HIV infection. CTLA‐4 was expressed only on T cells. Expression levels were significantly increased selectively on CD4+ T cells during all stages of HIV infection, while CTLA‐4 expression on CD8+ T cells was always low. In contrast, after stimulation with the mitogen phytohaemagglutinin (PHA), CTLA‐4 levels were strongly increased on T cells from controls but in T cells from HIV patients this response was severely impaired. Our data suggest that in HIV infection CD4+ and CD8+ T cells may be less responsive to B7 costimuli due to two different mechanisms: increase in CTLA‐4 expression by CD4+ cells and down‐regulation of CD28 by CD8+ cells.
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