Compartmentalized selection

The butyrophilin-like (Btnl) molecule Skint, which is expressed specifically by thymic epithelial cells and keratinocytes, is required for the selection of mouse V_γ5⁺ dendritic epidermal T cells. In Cell, Hayday and colleagues show that Btnl1 expressed by mouse enterocytes selectively promotes the maturation of intestinal V_γ7⁺ γδ T cells. The mouse gut supports the maturation and proliferation of CD122^hi V_γ7⁺ intraepithelial lymphocytes (IELs), a process that is independent of the thymus and the microbiota. Btnl1, Btnl4 and Btnl6 are expressed in the mouse small intestine. Btnl1^−/− mice, but not Btnl4^−/− mice, have highly selective loss of V_γ7⁺ IELs, whereas thymic V_γ7⁺T cells are not affected, and co-expression of Btnl1 and Btnl6 on gut epithelial cells in vitro specifically activates the V_γ7⁺ IELs. Human Btnl3 and Btnl8, which show enrichment on human epithelial cells in the gut, induce selective and T cell antigen receptor–dependent responses in V_γ4⁺ T cells, which dominate the γδ T cell compartment in human gut samples.

Cell (22 September 2016) 10.1016/j.cell.2016.08.030