Wang Heuy-Ching, Montufar-Solis Dina, Teng Ba-Bie, Klein John R
Department of Diagnostic Sciences, Dental Branch, University of Texas Health Science Center at Houston, 6516 M.D. Anderson Boulevard, Houston, TX 77030, USA.
J Immunol. 2004 Nov 15;173(10):6294-302. doi: 10.4049/jimmunol.173.10.6294.
CD43 has been linked to many function-associated T cell activities. Using mAbs that recognize two different CD43 determinants, we show that, although mouse small intestinal intraepithelial lymphocytes (IELs) expressed the CD43 core molecule reactive with mAb R2/60, only about one-half of the total IELs-including some but not all of the TCRalphabeta and TCRgammadelta cells-expressed the CD43 S7(-) reactive determinant. CD43 S7(+) IELs secreted more IL-2, IL-4, IL-10, IL-17, and IFN-gamma following anti-CD3 stimulation, and were >4-fold more cytotoxic in fresh isolates and >16-fold more cytotoxic after anti-CD3 stimulation, than S7(-) IELs. S7(+) but not S7(-) IELs from the ileum of IL-10(-/-) mice spontaneously produced IFN-gamma. In vivo BrdU uptake by IELs in non-Ag-primed mice was greatest in the S7(+) population, indicating that significantly more S7(+) IELs than S7(-) IELs undergo cell expansion under normal homeostatic conditions. DNA microarray analyses showed that S7(+) IELs expressed higher levels of genes associated with activated T cells, whereas S7(-) IELs expressed genes used in the regulation of NK cells. These findings define two functionally distinct populations of IELs based on CD43 expression independent of TCR class, and they identify a subset of IELs that may serve as a target to better control intestinal inflammation.
CD43与许多与功能相关的T细胞活动有关。使用识别两种不同CD43决定簇的单克隆抗体，我们发现，尽管小鼠小肠上皮内淋巴细胞（IEL）表达了与单克隆抗体R2/60反应的CD43核心分子，但在总的IEL中，只有大约一半（包括部分但不是全部的TCRαβ和TCRγδ细胞）表达了与CD43 S7(-)反应的决定簇。抗CD3刺激后，CD43 S7(+) IEL分泌更多的IL-2、IL-4、IL-10、IL-17和IFN-γ，并且在新鲜分离物中其细胞毒性比S7(-) IEL高4倍以上，抗CD3刺激后则高16倍以上。来自IL-10(-/-)小鼠回肠的S7(+)而非S7(-) IEL自发产生IFN-γ。在未接触抗原的小鼠中，IEL对体内BrdU的摄取在S7(+)群体中最高，这表明在正常稳态条件下，进行细胞扩增的S7(+) IEL比S7(-) IEL明显更多。DNA微阵列分析表明，S7(+) IEL表达与活化T细胞相关的基因水平更高，而S7(-) IEL表达用于调节NK细胞的基因。这些发现基于CD43表达定义了两个功能不同的IEL群体，且与TCR类别无关，并且它们鉴定出了一个IEL亚群，该亚群可能是更好地控制肠道炎症的靶点。
