Asymmetric cell division safeguards memory CD8 T cell development

Abstract

The strength of Tcell receptor (TCR) stimulation and asymmetric distribution of fate determinants are both implied to affect Tcell differentiation. Here, we uncover asymmetric cell division (ACD) as a safeguard mechanism for memory CD8 Tcell generation specifically upon strong TCR stimulation. Using live imaging approaches, we find that strong TCR stimulation induces elevated ACD rates, and subsequent single-cell-derived colonies comprise both effector and memory precursor cells. The abundance of memory precursor cells emerging from a single activated Tcell positively correlates with first mitosis ACD. Accordingly, preventing ACD by inhibition of protein kinase Cζ (PKCζ) during the first mitosis upon strong TCR stimulation markedly curtails the formation of memory precursor cells. Conversely, no effect of ACD on fate commitment is observed upon weak TCR stimulation. Our data provide relevant mechanistic insights into the role of ACD for CD8 Tcell fate regulation upon different activation conditions.