Origin, trafficking, and intraepithelial fate of gut-tropic T cells.
Origin, trafficking, and intraepithelial fate of gut-tropic T cells.
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DOI：
10.1084/jem.20122588
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发表时间：
2013-08-26
期刊：
影响因子：
--
通讯作者：
Bandeira A
中科院分区：
文献类型：
--
作者：
Guy-Grand D;Vassalli P;Eberl G;Pereira P;Burlen-Defranoux O;Lemaitre F;Di Santo JP;Freitas AA;Cumano A;Bandeira A
向小肠上皮细胞的趋向性是非常规和常规的近期胸腺移民的一般属性，但对于这两种细胞类型，只有GALT相关的循环胸导管淋巴细胞是细胞毒性上皮内淋巴细胞的前体。小肠上皮（SI-Ep）含有数百万非常规（γδ和CD 4 − CD 8 − NK1.1− TCRαβ）和常规（CD 8 αβ和CD 4）T细胞，称为上皮内淋巴细胞（IEL）。在这里，我们确定了SI-Ep-tropic T细胞的循环池，并研究了它们在稳态条件下在SPF小鼠中定殖SI-Ep的能力。α4β7的发育调节水平赋予非常规类型的近期胸腺移行细胞（RTEs）比其常规同源物具有更高的SI-Ep向性。SI-EP-tropic RTE，在所有谱系中出现幼稚，归巢SI-EP，但这种环境不足以刺激它们循环。相比之下，常规的和出乎意料的非常规的T细胞，特别是Vγ7+（γδ IEL的标志），先前在肠相关淋巴组织（GALT）中被刺激以循环，在SI-Ep中增殖。骑自行车的非常规SI-Ep移民比他们的传统同系物更有效地分裂，从而成为主导。这种差异影响了高颗粒酶B含量的获得，这需要广泛的增殖。总之，SI-亲Ep性T细胞遵循胸腺-SI-Ep或GALT-SI-Ep途径，后者产生高度竞争性的移民，是细胞毒性IEL的唯一前体。这些事件作为正常IEL动态的一部分连续发生。
Tropism to the small intestinal epithelium is a general property of unconventional and conventional recent thymic emigrants, but for both cell types only GALT-related cycling thoracic duct lymphocytes are the precursors of cytotoxic intraepithelial lymphocytes. The small intestine epithelium (SI-Ep) harbors millions of unconventional (γδ and CD4− CD8− NK1.1− TCRαβ) and conventional (CD8αβ and CD4) T cells, designated intraepithelial lymphocytes (IELs). Here, we identified the circulating pool of SI-Ep–tropic T cells and studied their capacity to colonize the SI-Ep under steady-state conditions in SPF mice. Developmentally regulated levels of α4β7 endowed recent thymic emigrants (RTEs) of unconventional types with higher SI-Ep tropism than their conventional homologues. SI-Ep–tropic RTEs, which in all lineages emerged naive, homed to the SI-Ep, but this environment was inadequate to stimulate them to cycle. In contrast, conventional and, unexpectedly, unconventional T cells, particularly Vγ7+ (hallmark of γδ IELs), previously stimulated to cycle in the gut-associated lymphoid tissue (GALT), proliferated in the SI-Ep. Cycling unconventional SI-Ep immigrants divided far more efficiently than their conventional homologues, thereby becoming predominant. This difference impacted on acquisition of high Granzyme B content, which required extensive proliferation. In conclusion, SI-Ep–tropic T cells follow a thymus–SI-Ep or a GALT–SI-Ep pathway, the latter generating highly competitive immigrants that are the sole precursors of cytotoxic IELs. These events occur continuously as part of the normal IEL dynamics.
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DOI：
10.1084/jem.172.1.239
发表时间：
1990-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bandeira A;Mota-Santos T;Itohara S;Degermann S;Heusser C;Tonegawa S;Coutinho A
通讯作者：
Coutinho A
影响因子：
15.9
作者：
GUYGRAND, D;VASSALLI, P
通讯作者：
VASSALLI, P
影响因子：
8
作者：
通讯作者：
--
影响因子：
5.4
作者：
GuyGrand, D;CuenodJabri, B;Vassalli, P
通讯作者：
Vassalli, P
影响因子：
64.8
作者：
HEILIG, JS;TONEGAWA, S
通讯作者：
TONEGAWA, S