Crosstalk between adaptive and innate immune cells leads to high quality immune protection at the mucosal borders.

Mucosal effector memory CD8 T cells are located at the epithelium and have a heightened and immediate effector function. By contrast, central memory T cells reside within lymphoid tissues and require proliferation and differentiation to become effector cells that migrate to epithelial surfaces. The accumulation of effector memory T cells at the pathogen entry site(s) is essential for protective immunity, but the mechanisms that drive the differentiation of memory cell subsets are poorly understood. We recently showed that CD8αα, induced selectively on the most highly activated primary CD8αβ T cells, together with its ligand, the thymic leukemia (TL) antigen, induced on mucosal antigen-presenting cells and constitutively expressed on intestinal epithelial cells (IEC), serve as key components to mediate the selective accumulation of the fittest effector cells to form mucosal effector memory T cells. Therefore, the generation of mucosal effector memory is controlled by an innate-adaptive crosstalk that provides for host defense at the body's largest interface.