Anti-CD3 induces bi-phasic apoptosis in murine intestinal epithelial cells: possible involvement of the Fas/Fas ligand system in different T cell compartments
Anti-CD3 induces bi-phasic apoptosis in murine intestinal epithelial cells: possible involvement of the Fas/Fas ligand system in different T cell compartments
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DOI：
10.1093/intimm/dxh231
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Hayakawa, S
中科院分区：
文献类型：
--
作者：
Miura, N;Yamamoto, M;Hayakawa, S
近年来的研究表明Fas介导的细胞凋亡参与了肠损伤的发病机制。在这项研究中，我们确定了Fas/Fas配体（FasL）的相互作用，在不同的T细胞隔室使用小鼠模型的小肠损伤的作用。腹腔注射145 - 2C11（抗CD3）抗体到C3H/HeN，BALB/c和MRL小鼠诱导粘膜扁平化和快速，双相肠上皮细胞（IEC）凋亡，这是通过常规的光学和电子显微镜和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记检测。在第一，早期阶段，绒毛细胞凋亡观察到注射后4小时，在第二，后期阶段，凋亡的隐窝细胞逐渐积累长达24小时。与对照株相比，lpr/lpr和裸小鼠的早期和晚期凋亡减少。此外，Fas介导的杀伤活性的动力学诱导的抗体注射肠上皮内淋巴细胞（IEL）和脾细胞（SPL）之间是不同的，似乎与双相发生的凋亡。最后，肠IEL从正常胸腺转移到裸鼠诱导两个阶段的细胞凋亡，而SPL诱导的第二阶段的隐窝凋亡只有通过注射抗体。总之，这些结果表明参与Fas介导的杀伤活性的胸腺衍生的T细胞在不同的隔间。也就是说，在不同的隔室中的T细胞群体差异参与诱导IEC凋亡，并有助于免疫介导的肠损伤的复杂发病机制，其中Fas/FasL相互作用可能发挥关键作用。
Recent studies have suggested that Fas-mediated apoptosis is involved in the pathogenesis of intestinal injury. In this study, we determined the role of Fas/Fas ligand (FasL) interactions in different T cell compartments using a murine model of small intestinal injury. An intraperitoneal injection of 145-2C11 (anti-CD3) antibody into C3H/HeN, BALB/c and MRL mice induced mucosal flattening and rapid, bi-phasic intestinal epithelial cell (IEC) apoptosis, which was detected by conventional light and electron microscopy and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. In the first, early phase, villous apoptosis was observed up to 4 h after injection, and in the second, later phase, apoptotic crypt cells gradually accumulated for up to 24 h. The early and later phases of apoptosis were reduced in lpr/lpr and nude mice compared with those in control strains. In addition, the kinetics of Fas-mediated killer activity induced by the antibody injection were different between intestinal intraepithelial lymphocytes (IEL) and splenocytes (SPL) and seemed to correlate with the bi-phasic occurrence of the apoptosis. Finally, the transfer of intestinal IEL from euthymic to nude mice induced both phases of apoptosis, whereas SPL induced the second phase's crypt apoptosis only by the antibody injection. Together, these results suggest the involvement of Fas-mediated killer activity of thymus-derived T cells in different compartments. Namely, T cell populations in different compartments are differentially involved in the induction of IEC apoptosis and contribute to the complex pathogenesis of immune-mediated intestinal injury in which Fas/FasL interactions may play a critical role.