S 1.6 ‐ Effector Functions and Complement

Abstract

Natural Killer (NK) cells contribute to a variety of innate immune responses to viruses, tumors and allogeneic cells. To study NK cell function, we compared gene expression profiles at the whole genome level between NK cells and other leukocyte subsets. Using this strategy, we identified NKp46 as the most specific NK cell transcript. By means of the NKp46 promoter, we generated transgenic mice expressing EGFP and the diphtheria toxin (DT) receptor in NK cells (NDE mice). DT injection in these mice leads to a complete and selective NK cell ablation. We used this model to revisit the stages of NK cell differentiation. Three subsets of mouse Natural Killer (NK) cells have been previously described: CD11b low CD27 high , CD11b high CD27 high and CD11b high CD27 low . To determine the developmental relationship between these subsets, we performed adoptive transfer of sorted subsets and also monitored the phenotype of developing EGFP + NK cells in NDE mice following DT injection. The results of these various experiments collectively support a four-stage model of NK cell maturation CD11b low /CD27 low -G CD11b low /CD27 high -G CD11b high /CD27 high -G CD11b high /CD27 low . We also used microarray analyses to mine for functional differences between NK cell subsets. The results of these experiments point to important differences in the trafficking, the turnover and the effector functions of the four NK cell subsets.