Down-regulation of the invariant Vα14 antigen receptor in NKT cells upon activation
Down-regulation of the invariant Vα14 antigen receptor in NKT cells upon activation
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DOI：
10.1093/intimm/dxh023
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发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Taniguchi, M
中科院分区：
文献类型：
--
作者：
Harada, M;Seino, K;Taniguchi, M
表达不变Valpha14抗原受体的NKT细胞构成了具有免疫调节功能的新型淋巴细胞亚群。通过其不变的Valpha14受体与抗cd3或配体α -半乳糖神经酰胺（α - galcer）的刺激，触发Valpha14 NKT细胞的激活，导致细胞因子如ifn - γ和IL-4的快速产生。受体激活后不久，通过加载α - galcer的CD1d四聚体（α - galcer /CD1d四聚体）染色判断，Valpha14 NKT细胞消失，这被认为是由于细胞凋亡死亡。在这里，我们发现这种消失主要归因于下调Valpha14受体。事实上，与传统的T细胞相比，Valpha14 NKT细胞具有相对的抗凋亡能力，这可以通过较少的Annexin-V染色，有限的DNA片段化以及抗凋亡基因如NAIP和MyD118的优先表达来证明。此外，即使在受体下调后，它们也不会产生耐受性，并保持其增殖能力和细胞因子的产生。这些尚未被认识的方面的Valpha14 NKT细胞讨论与其调控功能的关系。
NKT cells expressing the invariant Valpha14 antigen receptor constitute a novel lymphocyte subpopulation with immunoregulatory functions. Stimulation via their invariant Valpha14 receptor with anti-CD3 or a ligand, alpha-galactosylceramide (alpha-GalCer), triggers activation of Valpha14 NKT cells, resulting in a rapid cytokine production such as IFN-gamma and IL-4. Soon after their receptor activation, Valpha14 NKT cells disappeared as judged by staining with CD1d tetramer loaded with alpha-GalCer (alpha-GalCer/CD1d tetramer), which has been believed to be due to apoptotic cell death. Here we show that such a disappearance was largely attributed to down-regulation of the Valpha14 receptor. In fact, Valpha14 NKT cells were relatively resistant to apoptosis compared to the conventional T cells as evidenced by less staining with Annexin-V, a limited DNA fragmentation, and their preferential expression of anti-apoptotic genes such as NAIP and MyD118. Furthermore, they did not become tolerant, and maintained their proliferative capacity and cytokine production even after their receptor down-regulation. These as yet unrecognized facets of Valpha14 NKT cells are discussed in relation to their regulatory functions.