Mechanistic Assessment of PD-1H Coinhibitory Receptor-Induced T Cell Tolerance to Allogeneic Antigens.

Mechanistic Assessment of PD-1H Coinhibitory Receptor-Induced T Cell Tolerance to Allogeneic Antigens.
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DOI:
10.4049/jimmunol.1402648
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发表时间:
2015-06-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Chen L
Chen L
中科院分区:
其他
文献类型:
--
作者:
Flies DB;Higuchi T;Chen L

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PD-1H是新近发现的B7/CD28免疫调节基因家族的细胞表面共抑制分子。我们之前的研究表明,单次注射PD-1H激动型单抗(MAb)可以保护小鼠免受移植物抗宿主病(GVHD)的感染。我们在此报告了PD-1H诱导T细胞耐受的两种不同机制。首先,通过PD-1H共抑制受体的信号有效地阻止同种反应性供者T细胞在起始阶段的激活和扩增。其次,供体调节性T细胞随后被扩增,以维持长期耐受和GVHD抑制。我们的研究揭示了PD-1H作为同种反应性T细胞的共抑制受体的关键作用及其在调节T细胞耐受性中的作用。因此,PD-1H可能是GVHD和移植中调节同种异体反应性T细胞的靶点。
PD-1H is a recently identified cell surface co-inhibitory molecule of the B7/CD28 immune modulatory gene family. We showed previously that single injection of a PD-1H agonistic monoclonal antibody (mAb) protected mice from graft versus host disease (GVHD). We report here two distinct mechanisms operate in PD-1H-induced T cell tolerance. First, signaling via PD-1H co-inhibitory receptor potently arrests allo-reactive donor T cells from activation and expansion in the initiation phase. Second, donor regulatory T cells are subsequently expanded to maintain long-term tolerance and GVHD suppression. Our study reveals the crucial function of PD-1H as a co-inhibitory receptor on allo-reactive T cells and its function in the regulation of T cell tolerance. Therefore, PD-1H may be a target for the modulation of allo-reactive T cells in GVHD and transplantation.
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