title: Origin, trafficking, and intraepithelial fate of gut-tropic T cells.
abstract: 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.
authors.affiliation: Unité de Lymphopoièse, Institut Pasteur, Paris, France. guygrand@pasteur.fr
authors.forename: Delphine
authors.initials: D
authors.lastname: Guy-Grand
authors.forename: Pierre
authors.initials: P
authors.lastname: Vassalli
authors.forename: Gerard
authors.initials: G
authors.lastname: Eberl
authors.forename: Pablo
authors.initials: P
authors.lastname: Pereira
authors.forename: Odile
authors.initials: O
authors.lastname: Burlen-Defranoux
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lemaitre
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
authors.forename: Antonio A
authors.initials: AA
authors.lastname: Freitas
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
authors.forename: Antonio
authors.initials: A
authors.lastname: Bandeira
mesh_terms: D000818:Animals; D002455:Cell Division; D019070:Cell Lineage / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D004848:Epithelium / Q000276:immunology*; D053804:Granzymes / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology*; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D054388:Receptors, CCR / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013897:Thoracic Duct / Q000166:cytology; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development
chemical_list: C119309:CC chemokine receptor 9; D016023:Integrins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054388:Receptors, CCR; C071777:integrin alpha4beta7; D053804:Granzymes
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