Asymmetric cell division safeguards memory CD8 T cell development
A recent ‘Cell Reports’ paper by Gräbnitz and colleagues from the Oxenius group reports that ACD safeguards the generation of memory CD8 T cells upon strong TCR activation, revealing new mechanistic insights into fate diversification of CD8 T cells - an essential hallmark of adaptive immunity.
The strength of T cell receptor (TCR) stimulation and asymmetric distribution of fate determinants are both implied to affect T cell differentiation. Here, Gräbnitz et al. uncover asymmetric cell division (ACD) as a safeguard mechanism for memory CD8 T cell generation specifically upon strong TCR stimulation. Using live imaging approaches, they 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 T cell positively correlates with first mitosis ACD. Accordingly, preventing ACD by inhibition of 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. These data provide relevant mechanistic insights into the role of ACD for CD8 T cell fate regulation upon different activation conditions.
Link to the publication in external page "Cell Reports".