ACTIVATION OF LAMINA PROPRIA T-CELLS INDUCES CRYPT EPITHELIAL PROLIFERATION AND GOBLET CELL DEPLETION IN CULTURED HUMAN FETAL COLON

ACTIVATION OF LAMINA PROPRIA T-CELLS INDUCES CRYPT EPITHELIAL PROLIFERATION AND GOBLET CELL DEPLETION IN CULTURED HUMAN FETAL COLON
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DOI:
10.1136/gut.33.2.230
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发表时间:
1992-02-01
期刊:
GUT
影响因子:
24.5
通讯作者:
MACDONALD, TT
MACDONALD, TT
中科院分区:
医学1区
文献类型:
--
作者:
EVANS, CM;PHILLIPS, AD;MACDONALD, TT

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一个器官培养模型已经被用来研究T细胞激活在人类结肠中的作用。用商陆有丝分裂原或抗cd3单克隆抗体原位激活人胎儿结肠(妊娠11 ~ 23周)外植体培养的固有层T细胞,并与未刺激的对照组进行比较。培养3天后,在妊娠超过15周的T细胞刺激外植体中,隐窝上皮细胞增殖增加了2 - 4倍,与此同时,隐窝杯状细胞数量减少了20倍。第3天,受刺激的外植体表面上皮变薄,杯状细胞丢失,第7天,光镜和电镜观察到粘膜严重而广泛的损伤。这些变化在对照培养物和缺乏T细胞的外植体(妊娠少于16周)中没有发生,并且被环孢素a抑制。这些实验表明,慢性炎症性肠病患者结肠隐窝上皮细胞增殖的增加和伴随的杯状细胞耗散可能是由活化的T细胞介导的。
An organ culture model has been used to study the effects of T cell activation in the human colon. Lamina propria T cells in explant cultures of human fetal colon (11 to 23 weeks gestation) were activated in situ using pokeweed mitogen or an anti-CD3 monoclonal antibody, and compared with unstimulated controls. After three days of culture, there was a two to four-fold increase in crypt epithelial cell proliferation in T cell stimulated explants of more than 15 weeks gestation, associated with a fall in crypt goblet cell numbers of up to 20-fold. By three days, the surface epithelium of stimulated explants appeared thin with loss of goblet cells, and by day 7, severe and extensive mucosal damage was observed by light and electron microscopy. These changes did not occur in control cultures and explants deficient in T cells (less than 16 weeks gestation), and were inhibited by cyclosporin A. These experiments indicate that the increase in epithelial cell proliferation and accompanying goblet cell depletion observed in colorectal crypts in chronic inflammatory bowel disease may be mediated by activated T cells.