Engagement of NKG2D by cognate ligand or antibody alone is insufficient to mediate costimulation of human and mouse CD8+ T cells

Engagement of NKG2D by cognate ligand or antibody alone is insufficient to mediate costimulation of human and mouse CD8+ T cells
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DOI:
10.4049/jimmunol.174.4.1922
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发表时间:
2005-02-15
影响因子:
4.4
通讯作者:
Lanier, LL
Lanier, LL
中科院分区:
医学2区
文献类型:
--
作者:
Ehrlich, LIR;Ogasawara, K;Lanier, LL

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除了 TCR 参与之外,CD8+ T 细胞还需要通过共刺激受体的信号才能被激活。 CD28 在共刺激 T 细胞激活中的作用已得到充分证实。 NKG2D 是一种在 NK 细胞、CD8(+) Alpha-TCR+ T 细胞和 gammadelta-TCR+ T 细胞上发现的受体,也与 T 细胞共刺激有关。在这项研究中,我们评估了 NKG2D 在共刺激小鼠和人类初始和效应 CD8(+) T 细胞中的作用。出乎意料的是,与CD28相比,NKG2D与配体或mAb的结合不足以共刺激常规T细胞群中的幼稚或效应CD8(+) T细胞反应。虽然NKG2D本身不能共刺激CD8+T细胞,但它能够在某些条件下改变CD28介导的人类CD8+T细胞的共刺激。因此,NKG2D 很可能仅在受限条件下或需要额外的辅助因子时才充当共刺激分子。
CD8(+) T cells require a signal through a costimulatory receptor in addition to TCR engagement to become activated. The role of CD28 in costimulating T cell activation is well established. NKG2D, a receptor found on NK cells, CD8(+) alphabeta-TCR+ T cells, and gammadelta-TCR+ T cells, has also been implicated in T cell costimulation. In this study we have evaluated the role of NKG2D in costimulating mouse and human naive and effector CD8(+) T cells. Unexpectedly, in contrast to CD28, NKG2D engagement by ligand or mAb is not sufficient to costimulate naive or effector CD8(+) T cell responses in conventional T cell populations. While NKG2D did not costimulate CD8(+) T cells on its own, it was able to modify CD28-mediated costimulation of human CD8(+) T cells under certain contitions. It is, therefore, likely that NKG2D acts as a costimulatory molecule only under restricted conditions or requires additional cofactors.