Characterization of CD4+ CTLs ex vivo

Characterization of CD4+ CTLs ex vivo
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DOI:
10.4049/jimmunol.168.11.5954
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发表时间:
2002-06-01
影响因子:
4.4
通讯作者:
Kelleher, AD
Kelleher, AD
中科院分区:
医学2区
文献类型:
--
作者:
Appay, V;Zaunders, JJ;Kelleher, AD

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CD8(+)T细胞和NK细胞的细胞毒性潜能在对病原体的免疫应答中起着至关重要的作用。尽管体外研究已经报道了CD4(+)T细胞也能够介导穿孔素介导的杀伤,但细胞毒性CD4(+)T细胞的体内存在和相关性一直是争论的主题。在这里,我们表明,CD4(+)穿孔素(+)T细胞的人口是目前在健康的捐助者在循环中的低数量,并显着扩大与慢性病毒感染,特别是HIV感染,在疾病的所有阶段,包括早期原发性感染的捐助者。离体分析表明,这些细胞具有通过释放穿孔素介导的细胞毒性潜力。与更经典的CD4(+)T细胞相比,该亚群显示出与终末期分化的T细胞最一致的独特表面表型和功能特征,并且包括Ag经历的CD4(+)T细胞。在慢性病毒感染中,CD4(+)细胞毒性T细胞在体内以相对较高的水平存在,表明其在免疫应答中发挥作用。
The cytotoxic potential of CD8(+) T cells and NK cells plays a crucial role in the immune response to pathogens. Although in vitro studies have reported that CD4(+) T cells are also able to mediate perforin-mediated killing, the in vivo existence and relevance of cytotoxic CD4(+) T cells have been the subject of debate. Here we show that a population of CD4(+) perforin(+) T cells is present in the circulation at low numbers in healthy donors and is markedly expanded in donors with chronic viral infections, in particular HIV infection, at all stages of the disease, including early primary infection. Ex vivo analysis shows that these cells have cytotoxic potential mediated through the release of perforin. In comparison with more classical CD4(+) T cells, this subset displays a distinct surface phenotype and functional profile most consistent with end-stage differentiated T cells and include Ag experienced CD4(+) T cells. The existence of CD4(+) cytotoxic T cells in vivo at relatively high levels in chronic viral infection suggests a role in the immune response.