Abstract
SummaryThe induction and maintenance of T cell memory is critical to the success of vaccines. A recently described subset of memory CD8+ T cells defined by intermediate expression of the chemokine receptor CX3CR1 was shown to have self-renewal, proliferative, and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells when 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 early memory. In humans, CX3CR1int CD8+ T cells were strongly induced following adenovirus-vectored vaccination for hepatitis C virus (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 cells form an important component of the memory pool in response to persistent viruses and vaccines in both mice and humans.
Highlights
During an infection, naive T cells become activated and proliferate upon recognition of cognate antigen, giving rise to effector subsets
Intravenous (i.v.) infection of C57BL/6 mice with 106 plaque-forming unit (PFU) MCMV results in two distinct CD8+ T cell memory (Tmem) responses, the conventional and the expanded CD8+ T cell response in blood (Figure S1) (Bolinger et al, 2015)
Following i.v. injection of 106 PFU MCMV, three subsets based on CX3CR1 expression levels were distinguished in conventional and inflating CD8+ Tmem responses in blood (Figure 1A)
Summary
Naive T cells become activated and proliferate upon recognition of cognate antigen, giving rise to effector subsets. Tmem cells are heterogeneous subsets defined by homing receptor expression and tissue localization. Two major Tmem subsets in blood were defined based on expression of lymph node homing receptors CCR7 and CD62L, denoting CCR7+/CD62L+ central-memory (TCM) cells, with the capacity to migrate to lymphoid tissues, and CCR7À/CD62LÀ effector-memory (TEM) cells, which are able to migrate to peripheral tissues (Sallusto et al, 1999). TEM cells are more cytotoxic, migrate to diverse peripheral tissues sites, and until recently, were thought to be the dominant subset performing tissue surveillance (Sallusto et al, 1999). Non-migratory tissue-resident memory (TRM) cells, a third Tmem subset, are localized in diverse tissue sites and mediate local protective immune responses (Mueller and Mackay, 2016)
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