Xu Honglin, Chun Taehoon, Colmone Angela, Nguyen Hanh, Wang Chyung-Ru
Gwen Knapp Center for Lupus and Immunology Research, Committee on Immunology and Department of Pathology, University of Chicago, Chicago, IL 60637-5420, USA.
J Immunol. 2003 Oct 15;171(8):4105-12. doi: 10.4049/jimmunol.171.8.4105.
Although CD1d and MHC class Ia share similar overall structure, they have distinct levels and patterns of surface expression. While the expression of CD1d1 is known to be essential for the development of NKT cells, the contribution of CD1d1 to the development of CD8(+) T cells appears to be inconsequential. To investigate whether CD1d tissue distribution and expression levels confer differential capacity in selecting these two T cell subsets, we analyzed CD8 and NKT cell compartments in K(b)-CD1d-transgenic mice that lack endogenous MHC class Ia and CD1d, respectively. We found that MHC class Ia-like expression pattern and tissue distribution are not sufficient for CD1d to rescue the development of CD8(+) T cells, suggesting that unique structural features of CD1d preclude its active participation in selection of CD8(+) T cells. Conversely, cell type-specific CD1d surface density is important for the selection of NKT cells, as the NKT cell compartment was only partially rescued by the K(b)-CD1d transgene. We have previously demonstrated that increased CD1d expression on dendritic cells enhanced negative selection of NKT cells. In this study, we show that cell type-specific expression levels of CD1d establish a narrow window between positive and negative selection, suggesting that the distinct CD1d expression pattern may be selected evolutionarily to ensure optimal output of NKT cells.
尽管CD1d与MHC I类分子具有相似的整体结构，但它们在表面表达水平和模式上存在差异。虽然已知CD1d1的表达对于NKT细胞的发育至关重要，但CD1d1对CD8(+) T细胞发育的贡献似乎并不重要。为了研究CD1d的组织分布和表达水平是否在选择这两种T细胞亚群时赋予不同的能力，我们分析了分别缺乏内源性MHC I类分子和CD1d的K(b)-CD1d转基因小鼠中的CD8和NKT细胞区室。我们发现，MHC I类分子样的表达模式和组织分布不足以使CD1d挽救CD8(+) T细胞的发育，这表明CD1d独特的结构特征使其无法积极参与CD8(+) T细胞的选择。相反，细胞类型特异性的CD1d表面密度对于NKT细胞的选择很重要，因为K(b)-CD1d转基因仅部分挽救了NKT细胞区室。我们之前已经证明，树突状细胞上CD1d表达的增加增强了NKT细胞的阴性选择。在本研究中，我们表明CD1d的细胞类型特异性表达水平在阳性和阴性选择之间建立了一个狭窄的窗口，这表明独特的CD1d表达模式可能是在进化过程中被选择的，以确保NKT细胞的最佳输出。
