Induction and maintenance of CX3CR1-intermediate peripheral memory CD8 T cells by persistent viruses and novel vaccines

Abstract

The induction and maintenance of T-cell memory is critical to the success of novel vaccines. A newlydescribed subset of memory CD8 T-cells defined by intermediate expression of the chemokine receptor CX3CR1, were shown to have self-renewal, proliferative and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells in situations where memory is sustained at high levels – memory “inflation” induced by cytomegalovirus (CMV) and adenovirus-vectored vaccines. In mice, both CMV and vaccine-induced inflationary T-cells showed sustained high levels of CX3R1int cells exhibiting an effector-memory phenotype, characteristic of inflationary pools. In humans, CX3CR1int CD8 T-cells were strongly induced following administration of an adenovirus-vectored vaccine for HCV (ChAd3-NSmut) and during natural CMV infection, and were associated with a memory phenotype similar to that in mice. These data indicate that CX3CR1int memory cells form a substantial component of the memory pool in response to persistent viruses and vaccines in both mouse and man.