Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs.
Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs.
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DOI：
10.4049/jimmunol.0900420
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Schluns KS
中科院分区：
文献类型：
--
作者：
Ma LJ;Acero LF;Zal T;Schluns KS
IL-15对肠上皮内淋巴细胞（IEL）的发育至关重要，其传递由称为反式呈递的独特机制介导。实质细胞在IL-15向IEL的反式呈递中起主要作用，但这种细胞类型的具体身份尚不清楚。为了研究肠上皮细胞（IEC）是否是涉及的实质细胞类型，生成了仅由IEC表达IL-15 R α的小鼠模型（Villin/IL-15 R α Tg）。IEC的IL-15 R α的排他性表达恢复了在IL-15 R α不存在时存在的CD 8 αα+TCRαβ+和CD 8 αα+TCRγδ+亚群中的所有缺陷。有趣的是，大部分IEL的恢复是由于Thy 1 lo IEL的优先增加，这构成了IEL群体的大部分。发现Thy 1hiCD 4 − CD 8 −胸腺细胞分化为Thy 1 − CD 8 αα IEL需要IEC特异性表达IL-15 R α，因此提供了Thy 1 lo IEL分化是肠内IL-15反式呈递功能之一的证据。除了对IEL分化的影响外，IEC对IL-15的反式呈递也导致IEL数量增加，伴随着Bcl-2的增加，但不增殖。总的来说，本研究表明，IEC单独的IL-15反式呈递完全足以指导IL-15介导的IEL隔室内CD 8 αα+ T细胞群的发育，这包括新发现的IL-15在Thy 1 lo IEL分化中的作用。
IL-15 is crucial for the development of intestinal intraepithelial lymphocytes (IEL) and delivery is mediated by a unique mechanism known as trans-presentation. Parenchymal cells have a major role in the trans-presentation of IL-15 to IELs, but the specific identity of this cell type is unknown. To investigate whether the intestinal epithelial cells (IEC) are the parenchymal cell type involved, a mouse model that expresses IL-15Rα exclusively by the IECs (Villin/IL-15Rα Tg) was generated. Exclusive expression of IL-15Rα by the IECs restored all the deficiencies in the CD8αα+TCRαβ+and CD8αα+TCRγδ+ subsets that exist in the absence of IL-15Rα. Interestingly, most of the IEL recovery was due to the preferential increase in Thy1lo IELs, which compose a majority of the IEL population. The differentiation of Thy1hiCD4−CD8− thymocytes into Thy1−CD8αα IELs was found to require IL-15Rα expression specifically by IECs and thus, provides evidence that differentiation of Thy1lo IELs is one function of trans-presentation of IL-15 in the intestines. In addition to effects in IEL differentiation, trans-presentation of IL-15 by IECs also resulted in an increase in IEL numbers that was accompanied by increases in Bcl-2, but not proliferation. Collectively, this study demonstrates that trans-presentation of IL-15 by IECs alone is completely sufficient to direct the IL-15-mediated development of CD8αα+ T cell populations within the IEL compartment, which now includes a newly identified role of IL-15 in the differentiation of Thy1lo IELs.
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DOI：
10.1007/bf00783022
发表时间：
1988-01-01
期刊：
VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY
影响因子：
--
作者：
OSBORN, M;MAZZOLENI, G;WEBER, K
通讯作者：
WEBER, K
影响因子：
4.4
作者：
Masopust, D;Vezys, V;Ahmed, R
通讯作者：
Ahmed, R
DOI：
10.1084/jem.191.5.771
发表时间：
2000-03-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kennedy MK;Glaccum M;Brown SN;Butz EA;Viney JL;Embers M;Matsuki N;Charrier K;Sedger L;Willis CR;Brasel K;Morrissey PJ;Stocking K;Schuh JC;Joyce S;Peschon JJ
通讯作者：
Peschon JJ
影响因子：
4.4
作者：
Nakazato, Kenji;Yamada, Hisakata;Yoshikai, Yasunobu
通讯作者：
Yoshikai, Yasunobu
影响因子：
30.5
作者：
Lambolez, F;Arcangeli, ML;Ezine, S
通讯作者：
Ezine, S