Aswad Fred, Dennert Gunther
Department of Molecular Microbiology, USC/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Cell Immunol. 2006 Sep;243(1):58-65. doi: 10.1016/j.cellimm.2006.12.003. Epub 2007 Feb 6.
Contact of T lymphocytes with nicotinamide adenine dinucleotide (NAD) or ATP causes cell death that requires expression of purinergic receptor P2X(7) (P2X(7)R). T cell subsets differ in their responses to NAD and ATP, which awaits a mechanistic explanation. Here, we show that sensitivity to ATP correlates with P2X(7)R expression levels in CD4 cells, CD8 cells and CD4(+)CD25(+) cells from both C57BL/6 and BALB/c mice. But P2X(7)R ligands do not only induce cell death but also shedding of CD62L. It is shown here that in CD62L(high) T cells, CD62L shedding correlates with low expression of P2X(7)Rs and lower cell death, whereas in CD62L(low) cells P2X(7)R expression and death are higher. The possibility is therefore investigated that P2X(7)Rs induce T cell activation. Experiments show that spontaneous T cell proliferation is somewhat higher in cells expressing P2X(7)Rs, but this effect we suggest is caused by P2X(7)R expression on accessory cells.
T淋巴细胞与烟酰胺腺嘌呤二核苷酸(NAD)或三磷酸腺苷(ATP)接触会导致细胞死亡,这种细胞死亡需要嘌呤能受体P2X(7)(P2X(7)R)的表达。T细胞亚群对NAD和ATP的反应不同,这有待于作出机制上的解释。在此,我们表明,来自C57BL/6和BALB/c小鼠的CD4细胞、CD8细胞和CD4(+)CD25(+)细胞对ATP的敏感性与P2X(7)R表达水平相关。但是P2X(7)R配体不仅诱导细胞死亡,还会导致CD62L的脱落。本文表明,在CD62L(高)的T细胞中,CD62L的脱落与P2X(7)Rs的低表达及较低的细胞死亡相关,而在CD62L(低)的细胞中,P2X(7)R的表达和细胞死亡更高。因此,研究了P2X(7)Rs诱导T细胞活化的可能性。实验表明,在表达P2X(7)Rs的细胞中,自发的T细胞增殖略高,但我们认为这种效应是由辅助细胞上的P2X(7)R表达引起的。