It remains unclear if long-term immunological memory is maintained through stem cell–based–type mechanisms. In Immunity, Graef et al. investigate the multipotency, self-renewal and immune system–reconstituting ability of individual memory T cells through serial single-cell adoptive transfer and infection-induced population reexpansion. Single CD44hiCD62L+ central memory T cells (TCM cells) derived from transferred naive ovalbumin-specific OT-I T cells and sorted at least 100 days after infection with ovalbumin-expressing Listeria monocytogenes generate immune responses of a size, stochastic variation and phenotype (effector T cell, effector-memory T cell or TCM cell) similar to that generated by single naive T cells after secondary transfer. After repetitive single-cell adoptive transfer and infection-driven population reexpansion, primary and secondary TCM cells show broad proliferation and differentiation potential similar to that of naive T cells, and the tertiary progeny of two distinct secondary TCM cells are diverse and distinct. These results suggest that individual TCM cells have true self-renewal ability and are multipotent.

Immunity 41, 116–126 (2014)