NKp46+ CD3+ cells: a novel nonconventional T cell subset in cattle exhibiting both NK cell and T cell features.
NKp46+ CD3+ cells: a novel nonconventional T cell subset in cattle exhibiting both NK cell and T cell features.
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DOI：
10.4049/jimmunol.1302464
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发表时间：
2014-04-15
期刊：
影响因子：
--
通讯作者：
Morrison WI
中科院分区：
文献类型：
--
作者：
Connelley TK;Longhi C;Burrells A;Degnan K;Hope J;Allan AJ;Hammond JA;Storset AK;Morrison WI
NKp46受体表现出高度的谱系特异性，几乎只在自然杀伤细胞中表达。先前的研究已经证实NKp46可以通过t细胞表达，但NKp46+CD3+细胞非常罕见，并且几乎普遍与t细胞在刺激后获得NKp46相关。在这项研究中，我们证明了正常牛PBMC中存在NKp46+CD3+细胞群体，其中包括αβ TCR+和γδ TCR+谱系的细胞，并且以0.1-1.7%的频率存在。NKp46+CD3+细胞表达多种自然杀伤（NKR）和t细胞受体（TCR）的转录本，也表达CD3ζ、DAP10和FcεR1γ，但不表达DAP12衔接蛋白。对NKp46+CD3+细胞的体外功能分析证实，NKp46、CD16和CD3信号通路在功能上都是有效的，并且能够介导-再直接细胞溶解。然而，只有CD3交叉连接引起IFN-γ释放。NKp46+CD3+细胞在体外对自体细小梭菌感染的细胞表现出细胞毒活性，在体内感染该寄生虫期间，在一些动物中观察到NKp46+CD3+细胞的扩增，这表明这些细胞具有作为抗病原体效应群体的潜力。本文提出的结果鉴定并描述了一种新的非常规NKp46+CD3+ t细胞亚群，其表型和功能与传统NK细胞和t细胞不同。利用NKR和TCR的能力表明，这些细胞可能在先天和适应性免疫反应的界面上填补了功能龛。
The NKp46 receptor demonstrates a high degree of lineage-specificity, being expressed almost exclusively in natural killer cells. Previous studies have demonstrated NKp46 expression by T-cells, but NKp46+CD3+ cells are rare and almost universally associated with NKp46 acquisition by T-cells following stimulation. In this study we demonstrate the existence of a population of NKp46+CD3+ cells resident in normal bovine PBMC which include cells of both the αβ TCR+ and γδ TCR+ lineages and is present at a frequency of 0.1-1.7%. NKp46+CD3+ cells express transcripts for a broad repertoire of both natural killer (NKR) and T-cell receptors (TCR) and also the CD3ζ, DAP10 and FcεR1γ but not DAP12 adaptor proteins. In vitro functional analysis of NKp46+CD3+ cells confirm that NKp46, CD16 and CD3 signalling pathways are all functionally competent and capable of mediating-re-direct cytolysis. However, only CD3 cross-ligation elicits IFN-γ release. NKp46+CD3+ cells exhibit cytotoxic activity against autologous Theileria parva infected cells in vitro and during in vivo challenge with this parasite an expansion of NKp46+CD3+ cells was observed in some animals, indicating the cells have the potential to act as an anti-pathogen effector population. The results presented herein identifies and describes a novel non-conventional NKp46+CD3+ T-cell subset that is phenotypically and functionally distinct from conventional NK and T-cells. The ability to exploit both NKR and TCR suggests these cells may fill a functional niche at the interface of innate and adaptive immune responses.
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