Cutting Edge: Asymmetric Memory T Cell Division in Response to Rechallenge

Clonal selection of a T cell for use in the immune response appears to necessitate proliferative expansion and terminal effector differentiation of some cellular progeny, while reserving other progeny as less-differentiated memory cells. It has been suggested that asymmetric cell division may promote initial cell diversification. Stem cell-like models of adaptive immunity might predict that subsequent encounters with a pathogen would evoke reiterative, self-renewing, asymmetric division by memory T cells. In this study, we show that murine memory CD8(+) T cells can divide asymmetrically in response to secondary encounter with pathogen. Critical regulators of signaling and transcription are partitioned to one side of the mitotic spindle in rechallenged memory T cells, and two phenotypically distinct populations of daughter cells are evident from the earliest divisions. Memory T cells may thus use asymmetric cell division to generate cellular heterogeneity when faced with pathogen rechallenge.