KLF2 determines the susceptibility of T cells to immunoregulatory NK cells.

Natural killer (NK) cells suppress cellular and humoral immune responses via killing of T cells, resulting in diminished vaccine responses in mice and humans. Efforts to overcome this roadblock and achieve optimal immunity require an improved understanding of the molecular mediators facilitating NK cell-targeting of discrete subsets of CD4 T cells. We employed single-cell forensic victimology and CRISPR-Cas9 editing to delineate a transcriptional program uniquely responsible for the susceptibility of a subpopulation of CD4 T cells to perforin-dependent immunoregulation by NK cells.