Trans‐presentation of IL‐15 by intestinal epithelial cells drives development of CD8 alpha alpha T cells

Abstract

IL‐15, which is trans‐presented by IL‐15Rα+ cells to neighboring IL‐2Rβ/γC+ cells, is crucial for the development of intestinal intraepithelial lymphocytes (IEL). Parenchymal cells have a major role in the trans‐presentation of IL‐15 to IELs; however, the specific identity of this cell type is unknown. Since trans‐presentation requires cell‐cell contact, we hypothesize that intestinal epithelial cells (IEC) are the parenchymal cell trans‐presenting IL‐15 to IELs. To determine whether IECs trans‐present IL‐15 to developing IELs, we developed a mouse model with IL‐15Rα expressed exclusively by the IECs. This model was generated by driving IL‐15Rα under the Villin promoter and crossing to the IL‐15Rα−/− background. Analysis of these transgenic mice detected high levels of IL‐15Rα by the IECs. Among the IELs, Thy1‐ CD8αα TCRαβ and TCRγδ subsets were restored to normal or higher levels as compared to control and IL‐15Rα−/− mice. The increases in cell number did not appear to be the result of cell expansion as no differences in proliferation rate was detected among transgenic, control, or IL‐15Rα−/− mice. Collectively, this study demonstrates that IL‐15Rα expression by IECs alone is completely sufficient to direct all the IL‐15‐mediated events driving the development of CD8αα IELs. This research is supported by NIH grant AI070910 and the MDACC Trust Fellowship.