Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis.
Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis.
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DOI：
10.1084/jem.20092253
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发表时间：
2010-06-07
期刊：
影响因子：
--
通讯作者：
Cong Y
中科院分区：
文献类型：
--
作者：
Feng T;Wang L;Schoeb TR;Elson CO;Cong Y
微生物区系如何调控T细胞增殖，以及自发性T细胞增殖是否参与炎症性肠病的发病机制，目前还知之甚少。在这项研究中，我们发现微生物衍生的配体对先天通路的刺激和抗原特异性T细胞的刺激都是肠道炎症所必需的。微生物区系配体通过MyD88激活树突状细胞(DC)产生IL-6，从而促进T细胞的自发增殖，过继转移到无特定病原体的RAG−/−小鼠中的T细胞自发增殖，而在无菌RAG−/−小鼠中则不能。用盲肠细菌裂解物致敏的树突状细胞重建无菌RAG−/−小鼠，但不用IL-6−/−或MyD88−/−树突状细胞，恢复了自发的T细胞增殖。Cbir1TCR转基因(CBir1TG)T细胞对一种免疫优势微生物区系抗原具有特异性，可诱导SPF RAG−/−小鼠发生结肠炎。通过共转移大量OT II CD4+T细胞来阻断CBir1 TG T细胞的自发增殖，抑制了结肠炎的发生。尽管转移的OT II T细胞在RAG−/−小鼠体内自发增殖，但由于肠腔内缺乏同源抗原，受体未能发生结肠炎。总而言之，我们的数据表明，结肠炎的诱导既需要微生物区系固有信号驱动的T细胞的自发增殖，也需要抗原特异性T细胞的增殖。
Little is known about how the microbiota regulates T cell proliferation and whether spontaneous T cell proliferation is involved in the pathogenesis of inflammatory bowel disease. In this study, we show that stimulation of innate pathways by microbiota-derived ligands and antigen-specific T cell stimulation are both required for intestinal inflammation. Microbiota-derived ligands promoted spontaneous T cell proliferation by activating dendritic cells (DCs) to produce IL-6 via Myd88, as shown by the spontaneous proliferation of T cells adoptively transferred into specific pathogen–free (SPF) RAG−/− mice, but not in germfree RAG−/− mice. Reconstitution of germfree RAG−/− mice with cecal bacterial lysate–pulsed DCs, but not with IL-6−/− or Myd88−/− DCs, restored spontaneous T cell proliferation. CBir1 TCR transgenic (CBir1 Tg) T cells, which are specific for an immunodominant microbiota antigen, induced colitis in SPF RAG−/− mice. Blocking the spontaneous proliferation of CBir1 Tg T cells by co-transferring bulk OT II CD4+ T cells abrogated colitis development. Although transferred OT II T cells underwent spontaneous proliferation in RAG−/− mice, the recipients failed to develop colitis because of the lack of cognate antigen in the intestinal lumen. Collectively, our data demonstrate that induction of colitis requires both spontaneous proliferation of T cells driven by microbiota-derived innate signals and antigen-specific T cell proliferation.
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DOI：
10.1084/jem.20021387
发表时间：
2003-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barthlott T;Kassiotis G;Stockinger B
通讯作者：
Stockinger B
影响因子：
15.3
作者：
Goldrath, Ananda W;Sivakumar, Pallavur V;Glaccum, Moira;Kennedy, Mary K;Bevan, Michael J;Benoist, Christophe;Mathis, Diane;Butz, Eric A
通讯作者：
Butz, Eric A
影响因子：
24.5
作者：
Kobayashi, T.;Okamoto, S.;Hibi, T.
通讯作者：
Hibi, T.
影响因子：
4.4
作者：
Cong, YZ;Weaver, CT;Elson, CO
通讯作者：
Elson, CO
DOI：
10.1084/jem.2001889
发表时间：
2002-01-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iqbal N;Oliver JR;Wagner FH;Lazenby AS;Elson CO;Weaver CT
通讯作者：
Weaver CT