Transregulation of memory CD8 T-cell proliferation by IL-15Rα+ bone marrow–derived cells

Interleukin 15 (IL-15) and the IL-15 receptor alpha (IL-15Ralpha) chain are both required for the basal proliferation of memory CD8 T cells, but which cell types are required to express IL-15 or IL-15Ralpha to mediate this proliferation is not known. Using bone marrow (BM) chimeras, we showed that virus-specific CD8 memory T-cell proliferation was driven by IL-15 produced by either BM-derived or parenchymal cells. Experiments using mixed BM chimeras showed that IL-15Ralpha expression by memory CD8 T cells was not required for their division. In addition, wild-type memory CD8 T cells did not divide after transfer into IL-15Ralpha(-/-) mice. Further analyses demonstrated that IL-15Ralpha(+) BM-derived cells were crucial in driving memory CD8 T-cell division in the spleen while both parenchymal and BM-derived cells promoted memory cell division in the lung. Proliferation in response to soluble IL-15 in vivo required expression of IL-15Ralpha by opposing cells and IL-15Rbeta by CD8 memory cells, indicating that IL-15 interacted directly with the T cells. These results indicate that transpresentation of IL-15 by IL-15Ralpha on BM-derived cells mediates the basal proliferation of memory CD8 T cells.