Microbial colonization influences composition and T-cell receptor VP repertoire of intraepithelial lymphocytes in rat intestine

Microbial colonization influences composition and T-cell receptor VP repertoire of intraepithelial lymphocytes in rat intestine
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DOI:
10.1046/j.1365-2567.1996.d01-783.x
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发表时间:
1996-12-01
期刊:
影响因子:
6.4
通讯作者:
Brandtzaeg, P
Brandtzaeg, P
中科院分区:
医学2区
文献类型:
--
作者:
Helgeland, L;Vaage, JT;Brandtzaeg, P

文献摘要

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在小鼠身上的研究表明,肠道微生物定植可以显著改变肠道上皮内淋巴细胞(IEL)的组成。在一种大鼠模型中,利用无菌和常规动物,从小肠分离IEL并用流式细胞仪分析,研究了这种调节。T细胞受体(TCR)α/β(+)IEL的增殖和表型改变表现为T细胞受体(TCR)α/β(+)细胞的比例增加,而双阴性(CD4(-)CD8(-))细胞比例降低。微生物定植也影响CD8(+)IEL的TCR Vβ谱系,表现为Vβ8.2(+)和Vβ10(+)细胞比例增加,而Vβ8.5(+)和Vβ16(+)细胞比例相对降低。此外,常规化影响了相同Vβ亚群中TCR细胞表面的表达水平。三色流式细胞仪分析显示,Vβ谱系的偏斜在CD8α(+)亚群中最为明显,尽管IEL的数值增加主要包括CD8αβ(+)亚群。与IEL相比,肠道定植后肠系膜淋巴结的TCR Vβ谱系无明显变化。这些结果证实了TCRα/β(+)IEL亚群对微生物肠道菌群的动态反应,并表明它们的Vβ谱系可以由管腔微生物抗原塑造。
Studies in mice have shown that the composition of intestinal intraepithelial lymphocytes (IEL) may be markedly altered by gut microbial colonization. Such modulation was studied in a rat model by the use of germ-free and conventionalized animals from which IEL from the small intestine were isolated and analysed by flow cytometry. Conventionalization caused expansion as well as phenotypic alterations of T-cell receptor (TCR) alpha/beta(+) IEL in that the proportions of CD4(+) and CD8 alpha beta(+) TCR alpha/beta(+) cells were increased, while the double negative (CD4(-) CD8(-)) fraction was reduced. Microbial colonization also influenced the TCR V beta repertoire of CD8(+) IEL in that the proportions of V beta 8.2(+) and V beta 10(+) cells were increased, whereas V beta 8.5(+) and V beta 16(+) cells were relatively decreased. Moreover, conventionalization influenced the levels of TCR cell surface expression in the same V beta subsets. Three-colour flow-cytometric analysis demonstrated that skewing of the V beta repertoire was most pronounced in the CD8 alpha alpha(+) subset, although the numerical increase of IEL mainly included the CD8 alpha beta(+) subset. In contrast to IEL, the TCR V beta repertoire in mesenteric lymph nodes was unchanged after intestinal colonization. These results confirm that TCR alpha/beta(+) IEL subpopulations respond dynamically to the microbial gut flora and suggest that their V beta repertoire can be shaped by luminal microbial antigens.