Utilization of mouse models to decipher natural killer cell biology and potential clinical applications

Natural killer (NK) cells represent a key component of innate immunity. The utility of mouse models to recapitulate the human immune response has been a matter of ongoing debate, especially with regard to NK cells. However, mouse models of NK cells have provided significant advancements in our understanding of the biology of the cells that bridge these species. Initial characterization of NK cell activity was in mouse hematopoietic stem cell transplantation models. Recent findings include uncovering functionally disparate subsets of NK cells based on unique inhibitory receptor expression patterns, the existence of memory-like NK cells, and immunoregulatory NK cells that affect hematopoiesis and T-cell function. In addition, the biology of these cells with regard to MHC-binding receptors that affect NK cell subset maturation and function in the context of licensing, the importance of cytokines such as IL-15 in their development and maintenance, and evidence of NK exhaustion have been initially studied in mice. Many of these findings have been validated in clinical studies and demonstrate the significant wealth of knowledge that can be obtained by mouse models. However, it is important to understand the limitations and conditions of the mouse models, particularly when studying NK cells in hematopoietic stem cell transplantation and cancer.