Murine IL-2 outperforms human IL-2 in supporting the survival of naïve mouse CD8 T cells in vitro

Much of the immunology community relies on human IL-2 to support murine CD8 T-cell expansion in vitro. Although human and murine IL-2 share high similarity in amino acid sequence and exhibit similar biological activity, the potential cross-species implications of this practice remain largely unexamined, representing a significant yet overlooked variable in many in vitro studies that serve as the foundation of T-cell biology. Here, we compared the effects of human and murine IL-2 on CD8 T cells in vitro to uncover potential differences in T-cell biology. Murine IL-2 more effectively supported the survival of mouse naïve CD8 T cells in vitro and induced a distinct phenotype of IL-2 receptor expression on activated mouse CD8 T cells. In addition, murine IL-2 promoted enhanced antigen-independent expansion of memory-like CD8 T cells from naïve animals. Collectively, these findings should encourage laboratories to reevaluate their human IL-2 dosing strategies or consider transitioning to murine IL-2 for in vitro studies using murine CD8 T cells.