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Origin, trafficking, and intraepithelial fate of gut-tropic T cells

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 colo...

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Autores principales: Guy-Grand, Delphine, Vassalli, Pierre, Eberl, Gerard, Pereira, Pablo, Burlen-Defranoux, Odile, Lemaitre, Fabrice, Di Santo, James P., Freitas, Antonio A., Cumano, Ana, Bandeira, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754871/
https://www.ncbi.nlm.nih.gov/pubmed/23918956
http://dx.doi.org/10.1084/jem.20122588
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author Guy-Grand, Delphine
Vassalli, Pierre
Eberl, Gerard
Pereira, Pablo
Burlen-Defranoux, Odile
Lemaitre, Fabrice
Di Santo, James P.
Freitas, Antonio A.
Cumano, Ana
Bandeira, Antonio
author_facet Guy-Grand, Delphine
Vassalli, Pierre
Eberl, Gerard
Pereira, Pablo
Burlen-Defranoux, Odile
Lemaitre, Fabrice
Di Santo, James P.
Freitas, Antonio A.
Cumano, Ana
Bandeira, Antonio
author_sort Guy-Grand, Delphine
collection PubMed
description 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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spelling pubmed-37548712014-02-26 Origin, trafficking, and intraepithelial fate of gut-tropic T cells Guy-Grand, Delphine Vassalli, Pierre Eberl, Gerard Pereira, Pablo Burlen-Defranoux, Odile Lemaitre, Fabrice Di Santo, James P. Freitas, Antonio A. Cumano, Ana Bandeira, Antonio J Exp Med Article 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. The Rockefeller University Press 2013-08-26 /pmc/articles/PMC3754871/ /pubmed/23918956 http://dx.doi.org/10.1084/jem.20122588 Text en © 2013 Guy-Grand et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Guy-Grand, Delphine
Vassalli, Pierre
Eberl, Gerard
Pereira, Pablo
Burlen-Defranoux, Odile
Lemaitre, Fabrice
Di Santo, James P.
Freitas, Antonio A.
Cumano, Ana
Bandeira, Antonio
Origin, trafficking, and intraepithelial fate of gut-tropic T cells
title Origin, trafficking, and intraepithelial fate of gut-tropic T cells
title_full Origin, trafficking, and intraepithelial fate of gut-tropic T cells
title_fullStr Origin, trafficking, and intraepithelial fate of gut-tropic T cells
title_full_unstemmed Origin, trafficking, and intraepithelial fate of gut-tropic T cells
title_short Origin, trafficking, and intraepithelial fate of gut-tropic T cells
title_sort origin, trafficking, and intraepithelial fate of gut-tropic t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754871/
https://www.ncbi.nlm.nih.gov/pubmed/23918956
http://dx.doi.org/10.1084/jem.20122588
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