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


ABSTRACT: The small intestine epithelium (SI-Ep) harbors millions of unconventional (?? and CD4(-) CD8(-) NK1.1(-) TCR??) and conventional (CD8?? 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 ?4?7 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 V?7(+) (hallmark of ?? 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.

SUBMITTER: Guy-Grand D 

PROVIDER: S-EPMC3754871 | biostudies-other | 2013 Aug

REPOSITORIES: biostudies-other

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

Guy-Grand Delphine D   Vassalli Pierre P   Eberl Gerard G   Pereira Pablo P   Burlen-Defranoux Odile O   Lemaitre Fabrice F   Di Santo James P JP   Freitas Antonio A AA   Cumano Ana A   Bandeira Antonio A  

The Journal of experimental medicine 20130805 9


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 c  ...[more]

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