You can’t live forever — but perhaps your T cells can

Masopust and colleagues have found that memory CD8+ T cells can retain the capacity for cell division for longer than the lifespan of the host. Using an acute heterologous prime–boost–boost vaccination strategy, they generated an expanded tertiary population of long-lived memory CD8+ T cells in CD45.1+ C57Bl/6 mice. They transferred some of these memory T cells to naive congenic CD45.2+ recipients, gave the mice three further vaccinations (at least 60 days apart) and were able to continue with this transfer and triple challenge protocol for roughly ten years — the CD45.1+ T cell population never lost the capacity to expand, execute antimicrobial functions and form quiescent memory T cells after challenge. These iteratively stimulated T cells (ISTCs) maintained their telomere lengths and showed no loss of growth control, undergoing lower levels of homeostatic turnover than primary memory T cells. The ISTCs did show epigenetic and phenotypical changes over the course of the experiment. Notably, they lost markers associated with memory T cell ‘stemness’ and acquired expression of ‘exhaustion’ markers, such as PD1, TIM3 and TOX, despite not losing their capacity to respond to antigenic challenge.

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