Dianda L, Hanby A M, Wright N A, Sebesteny A, Hayday A C, Owen M J
Imperial Cancer Research Fund, London, United Kingdom.
Am J Pathol. 1997 Jan;150(1):91-7.
Mice with null mutations in cytokine or T cell receptor (TCR) genes develop intestinal inflammation. In the case of interleukin-2-/- and interleukin-10-/- mice it has been demonstrated that normal intestinal bacterial flora can cause gut pathology. TCR-alpha-/- mice not only develop colitis but also produce a strong antibody response to self-antigens, such as double-stranded DNA. It is therefore important to establish whether the intestinal inflammation develops spontaneously or is induced by luminal antigens. To address this issue, a germ-free colony of TCR-alpha-/- mice was derived and compared with TCR-alpha-/- mice kept in conventional specific-pathogen-free conditions. Although specific-pathogen-free animals developed colitis with a high level of penetrance, there was no evidence of intestinal pathology in germ-free animals. Furthermore, intestinal inflammation was not seen in TCR-alpha-/- mice colonized with a limited bacterial flora consisting of Lactobacillus plantarum, Streptococcus faecalis, S. faecium, and/or Escherichia coli. We conclude that intestinal inflammation in TCR-alpha-/- mice does not occur spontaneously nor does it result from the presence of bacteria, per se, but rather it is initiated by a specific organism or group of organisms normally present in the gut flora that have yet to be identified.
细胞因子或T细胞受体（TCR）基因发生无效突变的小鼠会出现肠道炎症。就白细胞介素-2基因敲除小鼠和白细胞介素-10基因敲除小鼠而言，已证实正常的肠道细菌菌群可导致肠道病变。TCR-α基因敲除小鼠不仅会发生结肠炎，还会对自身抗原（如双链DNA）产生强烈的抗体反应。因此，确定肠道炎症是自发产生还是由腔内抗原诱导产生很重要。为了解决这个问题，培育了一群无菌的TCR-α基因敲除小鼠，并将其与饲养在常规无特定病原体条件下的TCR-α基因敲除小鼠进行比较。尽管无特定病原体的动物发生结肠炎的发生率很高，但无菌动物没有肠道病变的迹象。此外，在用由植物乳杆菌、粪链球菌、屎肠球菌和/或大肠杆菌组成的有限细菌菌群定殖的TCR-α基因敲除小鼠中未观察到肠道炎症。我们得出结论，TCR-α基因敲除小鼠的肠道炎症既不是自发发生的，也不是由细菌本身的存在导致的，而是由正常存在于肠道菌群中尚未确定的特定一种或一组生物体引发的。
