Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases.

Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-γ production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors.

Skeletal muscle interleukin 15 promotes CD8(+) T-cell function and autoimmune myositis.

Background: Interleukin 15 (IL-15) is thought to be abundant in the skeletal muscle under steady state conditions based on RNA expression; however, the IL-15 RNA level may not reflect the protein level due to post-transcriptional regulation. Although exogenous protein treatment and overexpression studies indicated IL-15 functions in the skeletal muscle, how the skeletal muscle cell uses IL-15 remains unclear. In myositis patients, IL-15 protein is up-regulated in the skeletal muscle.

Adipocyte IL-15 regulates local and systemic NK cell development.

NK cell development and homeostasis require IL-15 produced by both hematopoietic and parenchymal cells. Certain hematopoietic IL-15 sources, such as macrophages and dendritic cells, are known, whereas the source of parenchymal IL-15 remains elusive. Using two types of adipocyte-specific Il15(-/-) mice, we identified adipocytes as a parenchymal IL-15 source that supported NK cell development nonredundantly.

IL-15Rα of radiation-resistant cells is necessary and sufficient for thymic invariant NKT cell survival and functional maturation.

The development of invariant NKT (iNKT) cells depends on the thymus. After positive selection by CD4(+)CD8(+)CD1d(+) cortical thymocytes, iNKT cells proceed from CD44(low)NK1.1(-) (stage 1) to CD44(high)NK1.

IL-15 does not affect IEL development in the thymus but regulates homeostasis of putative precursors and mature CD8 alpha alpha+ IELs in the intestine.

Mice devoid of the IL-15 system lose over 90% of CD8alphaalpha(+) TCRalphabeta and TCRgammadelta intestinal intraepithelial lymphocytes (iIELs). Previous work revealed that IL-15Ralpha and IL-15 expressed by parenchymal cells, but not by bone marrow-derived cells, are required for normal CD8alphaalpha(+) iIEL homeostasis. However, it remains unclear when and how the IL-15 system affects CD8alphaalpha(+) iIELs through their development.