Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor α expression

IL-15 and the IL-15 receptor (IL-15R)alpha chain are essential for normal development of naive CD8 T cells, intestinal intraepithelial lymphocytes (IEL), and natural killer (NK)/NK/T cells. However, whether IL-15Ralpha expression by these subsets is necessary for their production and which cell type needs to produce IL-15 to drive development are unknown. We analyzed the requirements for IL-15 and IL-15Ralpha expression by bone marrow-derived or parenchymal cells for mediating lymphocyte subset development. Naive CD8 T cell development required IL-15Ralpha expression by both bone marrow-derived and parenchymal cells, whereas memory-phenotype CD8 T cells required IL-15Ralpha expression only by hematopoietic cells. In contrast and surprisingly, the development of IEL subsets, particularly CD8alphaThy1(-)Vgamma5(+) T cell antigen receptor gammadelta and the CD8alphaalphaThy1(-) T cell antigen receptor alphabeta IEL populations, depended completely on parenchymal cell expression of IL-15Ralpha and IL-15 but not IL-15Rbeta. In the case of INK and NK/T cell generation and maturation, expression of IL-15 and IL-15Ralpha by both parenchymal and hematopoietic cells was important, although the latter played the greatest role. These results demonstrated dichotomous mechanisms by which IL-15 regulated lymphoid development, interacting with distinct cell types depending on the developmental pathway.