| First Author | Guy-Grand D | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 9 | Pages | 1839-54 |
| PubMed ID | 23918956 | Mgi Jnum | J:202497 |
| Mgi Id | MGI:5519186 | Doi | 10.1084/jem.20122588 |
| Citation | Guy-Grand D, et al. (2013) Origin, trafficking, and intraepithelial fate of gut-tropic T cells. J Exp Med 210(9):1839-54 |
| abstractText | The small intestine epithelium (SI-Ep) harbors millions of unconventional (gammadelta and CD4(-) CD8(-) NK1.1(-) TCRalphabeta) and conventional (CD8alphabeta 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 alpha4beta7 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 Vgamma7(+) (hallmark of gammadelta 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. |
