Regulation of NKT cells by Ly49: Analysis of primary NKT cells and generation of NKT cell line
Regulation of NKT cells by Ly49: Analysis of primary NKT cells and generation of NKT cell line
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DOI：
10.4049/jimmunol.167.8.4180
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发表时间：
2001-10-15
影响因子：
4.4
通讯作者：
Takei, F
中科院分区：
文献类型：
--
作者：
Maeda, M;Lohwasser, S;Takei, F
TCRα-β(+)NK1.1(+)(NKT)细胞表达多种NK细胞相关分子，包括MHC-I受体Ly49家族，但其功能意义尚不清楚。在这里，我们检测了Ly49A、C/I和G2在正常和MHC I类缺陷的C57BL/6小鼠不同NKT细胞群上的表达，以及它们对CD1d限制性NKT细胞的有效刺激因子α-半乳糖神经酰胺(α-GalCer)的反应性。不同组织来源的NKT细胞表达Ly49的频率和水平不同，并受宿主MHC I类分子和CD1d的表达调控。α-GalCer对多种NKT细胞的刺激表明，Ly49的表达与NKT细胞对α-GalCer的反应性呈负相关。此外，正常树突状细胞呈递的α-GalCer刺激纯化的Ly49(-)而不是Ly49(+)的脾NKT细胞，而MHC-I类缺陷树突状细胞对LY49(+)和Ly49-NKT细胞呈递同样好的α-GalCer。因此，APC表面的MHC-I类分子似乎抑制了表达Ly49的NKT细胞的激活。为了进一步鉴定CD1d限制性的NKT细胞，我们从胸腺细胞中获得了一个α-GalCer反应的NKT细胞系。该细胞系只能从LY49(-)NK1.1(+)CD4(+)胸腺细胞中产生，而不能从其他NKT细胞亚群中产生，并且在培养过程中失去了NK1.1和CD4的表达。综上所述，这些结果表明Ly49在NKT细胞上的表达具有功能意义。
TCR alpha beta (+)NK1.1(+) (NKT) cells are known to express various NK cell-associated molecules including the Ly49 family of receptors for MHC class I, but its functional significance has been unclear. Here, we examined the expression of Ly49A, C/I and G2 on various NKT cell populations from normal and MHC class I-deficient C57BL/6 mice as well as their responsiveness to a-galactosylceramide (alpha -GalCer), a potent stimulator of CD1d-restricted NKT cells. The frequency and the level of Ly49 expression varied among NKT cells from different tissues, and were regulated by the expression of MHC class I and CD1d in the host. Stimulation of various NKT cells with a-GalCer suggested that Ly49 expression inversely correlates with the responsiveness of NKT cells to alpha -GalCer. Moreover, alpha -GalCer presented by normal dendritic cells stimulated purified Ly49(-), but not Ly49(+), splenic NKT cells, whereas MHC class I-deficient dendritic cells presented alpha -GalCer to both LY49(+) and Ly49- NKT cells equally well. Therefore, MHC class I on APCs seems to inhibit activation of NKT cells expressing Ly49. To further characterize CD1d-restricted NKT cells, we generated an alpha -GalCer-responsive NKT cell line from thymocytes. The line could only be generated from LY49(-)NK1.1(+)CD4(+) thymocytes but not from other NKT cell subsets, and it lost expression of NK1.1 and CD4 during culture. Together, these results indicate the functional significance of Ly49 expression on NKT cells.