Abstract
Abstract The ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that T cell progression from the naïve to the memory state is an irreversible differentiation event. Here we report that unlike naïve T cells, which are in the G0 phase of the cell cycle, CD8+ memory T cells exist in a state of readiness in G1. This was maintained by occupancy of members the TNF receptor superfamily, CD27 and 4-1BB, which when disrupted caused memory T cells to revert to G0 and respond like naïve T cells to stimulation. Furthermore, maintenance of the G1 state was compromised in antigen-specific memory T cells of VSV-infected CD27-deficient mice. Manipulating the memory T cell state of readiness might benefit disorders involving chronic ongoing immune responses. This work was supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute