Distinct functional lineages of human V(alpha)24 natural killer T cells.
Distinct functional lineages of human V(alpha)24 natural killer T cells.
复制标题
人V（alpha）24天然杀伤T细胞的独特功能谱系。
DOI：
10.1084/jem.20011908
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发表时间：
2002-03-04
影响因子：
15.3
通讯作者：
Bendelac, Albert
中科院分区：
文献类型：
--
作者：
Lee, Peter T;Benlagha, Kamel;Teyton, Luc;Bendelac, Albert
据报道，CD 1d限制性自身反应性自然杀伤（NK）T细胞通过分泌辅助性T细胞（Th）2或Th 1细胞因子来调节一系列疾病，包括I型糖尿病和癌症的免疫排斥。然而，这些细胞分泌Th 2细胞因子与Th 1细胞因子的机制还不清楚。由于大多数健康受试者每1，000个外周血淋巴细胞（PBL）中表达<1个NKT细胞，我们设计了一种新的方法，该方法基于联合使用T细胞受体（TCR）特异性试剂α-半乳糖神经酰胺（αGalCer）负载的CD 1d-四聚体和抗V α24单克隆抗体，以特异性地鉴定和表征新鲜PBL中的这些稀有细胞。我们在此报告，CD 4+和CD 4 − CD 8 −（双阴性[DN]）NKT细胞亚群代表功能不同的谱系，其细胞因子分泌谱和趋化因子受体、整合素和NK受体表达模式存在显著差异。CD 4 + NKT细胞是白细胞介素（IL）-4和IL-13的唯一生产者，而DN NKT细胞具有严格的Th 1特征，并显著表达几种NK谱系受体。这些发现可能解释了NKT细胞如何在某些情况下促进Th 2应答，在其他情况下促进Th 1应答，并应考虑对相关疾病进行干预。
CD1d-restricted autoreactive natural killer (NK)T cells have been reported to regulate a range of disease conditions, including type I diabetes and immune rejection of cancer, through the secretion of either T helper (Th)2 or Th1 cytokines. However, mechanisms underlying Th2 versus Th1 cytokine secretion by these cells are not well understood. Since most healthy subjects express <1 NKT cell per 1,000 peripheral blood lymphocytes (PBLs), we devised a new method based on the combined used of T cell receptor (TCR)-specific reagents α-galactosylceramide (αGalCer) loaded CD1d-tetramers and anti-Vα24 monoclonal antibody, to specifically identify and characterize these rare cells in fresh PBLs. We report here that CD4+ and CD4−CD8− (double negative [DN]) NKT cell subsets represent functionally distinct lineages with marked differences in their profile of cytokine secretion and pattern of expression of chemokine receptors, integrins, and NK receptors. CD4+ NKT cells were the exclusive producers of interleukin (IL)-4 and IL-13 upon primary stimulation, whereas DN NKT cells had a strict Th1 profile and prominently expressed several NK lineage receptors. These findings may explain how NKT cells could promote Th2 responses in some conditions and Th1 in others, and should be taken into consideration for intervention in relevant diseases.