CD58/CD2 Is the Primary Costimulatory Pathway in Human CD28-CD8+ T Cells
CD58/CD2 Is the Primary Costimulatory Pathway in Human CD28-CD8+ T Cells
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DOI：
10.4049/jimmunol.1401917
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发表时间：
2015-07-15
影响因子：
4.4
通讯作者：
Steinberger, Peter
中科院分区：
文献类型：
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作者：
Leitner, Judith;Herndler-Brandstetter, Dietmar;Steinberger, Peter
成人中相当大比例的CD8(+) T细胞缺乏CD28分子的表达，免疫系统的衰老与这种T细胞亚群的稳定扩张有关。CD28(-) CD8(+) T细胞具有强大的效应功能，但对抗原攻击的反应受损。CD28作为主要的T细胞共刺激受体，但还有许多其他受体可以共刺激T细胞的激活。在这项研究中，我们研究了这些替代的共刺激途径在CD28(-) CD8(+) T细胞中的功能作用。我们的研究表明，大多数共刺激分子激活cd28缺陷T细胞的能力较低，而CD2分子与其配体CD58的结合明显地共刺激了该T细胞亚群的增殖、细胞因子的产生和效应功能。CD58在包括树突状细胞在内的apc上广泛表达。阻断CD58 mAb可大大降低人CD28(-) CD8(+) T细胞对异体树突状细胞和病毒Ags的反应。我们的研究结果清楚地确定了CD58/CD2轴是缺乏CD28的CD8 T细胞的主要共刺激途径。此外，我们发现CD2的参与放大了CD28(-) CD8(+) T细胞中的TCR信号，表明CD2- cd58的相互作用对这一T细胞亚群具有真正的共刺激作用。CD2信号可能促进CD28(-) CD8(+) T细胞对病毒感染的控制，但它们也可能有助于CD28(-) CD8(+) T细胞在持续银的慢性刺激下的持续扩增。
A substantial proportion of CD8(+) T cells in adults lack the expression of the CD28 molecule, and the aging of the immune system is associated with a steady expansion of this T cell subset. CD28(-) CD8(+) T cells are characterized by potent effector functions but impaired responses to antigenic challenge. CD28 acts as the primary T cell costimulatory receptor, but there are numerous additional receptors that can costimulate the activation of T cells. In this study, we have examined such alternative costimulatory pathways regarding their functional role in CD28(-) CD8(+) T cells. Our study showed that most costimulatory molecules have a low capacity to activate CD28-deficient T cells, whereas the engagement of the CD2 molecule by its ligand CD58 clearly costimulated proliferation, cytokine production, and effector function in this T cell subset. CD58 is broadly expressed on APCs including dendritic cells. Blocking CD58 mAb greatly reduced the response of human CD28(-) CD8(+) T cells to allogeneic dendritic cells, as well as to viral Ags. Our results clearly identify the CD58/CD2 axis as the primary costimulatory pathway for CD8 T cells that lack CD28. Moreover, we show that engagement of CD2 amplifies TCR signals in CD28(-) CD8(+) T cells, demonstrating that the CD2-CD58 interaction has a genuine costimulatory effect on this T cell subset. CD2 signals might promote the control of viral infection by CD28(-) CD8(+) T cells, but they might also contribute to the continuous expansion of CD28(-) CD8(+) T cells during chronic stimulation by persistent Ag.