Possible mechanisms of induction of apoptosis in enterocytes by intraepithelial lymphocytes.

本文报道了应用抗CD 3单克隆抗体（mAb）激活肠上皮内淋巴细胞（i-IELs）可诱导肠上皮细胞凋亡。为了阐明激活的i-IEL诱导肠细胞凋亡的机制，我们设计了实验，通过抗CD 3 mAb刺激IEL，并检查肠细胞的后续变化。在大鼠中，注射本实验室制备的抗CD 3 mAb（1F 4）后2小时，肠细胞出现大量DNA断裂30 mm，随后出现脱落。本实验通过免疫抑制剂FK 506对大鼠肠上皮细胞的抑制作用，分析肠上皮细胞的变化。每天给予FK 506灭活i-IELs可使绒毛中肠上皮细胞的凋亡消失。然后，在肠细胞中，长期每日给予FK 506导致氨基酸t的表达减少， ...更多信息 CD 98和碱性磷酸酶（ALP）活性。此外，这些处理诱导的消失和F-actin的肠上皮细胞的微绒毛的异质性表达。结果表明，每天给予FK 506灭活i-IEL可抑制肠上皮细胞的凋亡，提示肠上皮细胞在绒毛上残留了功能障碍的肠上皮细胞，而这些功能障碍的肠上皮细胞是导致凋亡的主要原因。裸鼠和scid小鼠肠上皮细胞氨基酸转运蛋白、CD 98的表达、ALP活性及与基底膜的粘附活性均下降，这与肠上皮细胞整合素α 6的表达下降有关。给予CD 3 mAb未能使这些免疫缺陷小鼠的上皮脱落并引起严重腹泻。因此，i-IEL可能在维护绒毛上的上皮细胞方面发挥重要作用。少

We reported that the administration of anti-CD3 monoclonal antibody (mAb) and subsequently activation of intestinal intra-epithelial lymphocytes (i-IELs) could induce apoptosis to enterocytes. To elucidate the mechanism of the induction of apoptosis in enterocytes by activated i-IELs, we designed experiments to stimulate the IEL by anti-CD3 mAb and to examine the subsequent changes to the enterocytes. In rats, the enterocytes showed massive DNA fragmentation 30 mm and subsequent detachment 2 hours after injection of anti-CD3 mAb (1F4) made in our laboratory. Then, we newly found the growth and hypertrophy of the goblet cells in rats.We designed experiments to inactivate the IEL by immunosuppressant, FK506 and to analyze the subsequent changes of the enterocytes. The inactivation of i-IELs by daily administration of FK506 disappeared apoptosis of enterocytes in villus. Then, in the enterocytes, the long term daily administration of FK506 caused decrease in the expression of amino acid t … More ransporter, CD98 and the activity of alkaline phosphatase (ALP). Furthermore, these treatments induced the disappearance and heterogenous expression of F-actin in microvilli of enterocytes. It showed that the inactivation of i-IELs by daily administration of FK506 could inhibit apoptosis in enterocytes, and these results suggested that the dysfunctional enterocytes, which should have been led to apoptosis, remained on the villus.With the immunodeficiency mice that decreased i-IEL, we analyzed morphological and functional changes in epithelial cells. The enterocytes in nude and scid mice decreased in the expression of amino acid transporter, CD98, the activity of ALP, and the adhesion activity with basement membrane due to the decline in the expression of integrin α_6 on the enterocytes. The administration of CD3 mAb failed to exfoliate the epithelium and cause severe diarrhea in these immunodeficiency mice. Therefore, i-IELs may have an important role in maintenance of epithelial cells on the villus. Less