Quantitative Difference in PLZF Protein Expression Determines iNKT Lineage Fate and Controls Innate CD8 T Cell Generation

Summary Zbtb16 encodes the zinc-finger protein PLZF, which is often used as a lineage marker for innate-like T cells and is specifically required for the generation of invariant natural killer T ( i NKT) cells in the thymus. Here, we report that not only PLZF expression itself but also the relative abundance of PLZF proteins plays critical roles in i NKT cell development. Utilizing a Zbtb16 hypomorphic allele, PLZF GFPCre , which produces PLZF proteins at only half of the level of the wild-type allele, we show that decreased PLZF expression results in a significant decrease in i NKT cell numbers, which is further associated with profound alterations in i NKT lineage choices and subset composition. These results document that there is a quantitative aspect of PLZF expression in i NKT cells, demonstrating that the availability of PLZF protein is a critical factor for both effective i NKT cell generation and subset differentiation.