Functional classification of memory CD8+ T cells by CX3CR1 expression

Localization of memory CD8 + T cells to lymphoid or peripheral tissues is believed to correlate with proliferative capacity or effector function. Here we demonstrate that the fractalkine-receptor/CX 3 CR1 distinguishes memory CD8 + T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties. CX 3 CR1-based transcriptome and proteome-profiling defines a core signature of memory CD8 + T cells with effector function. We find CD62L hi CX 3 CR1 + memory T cells that reside within lymph nodes. This population shows distinct migration patterns and positioning in proximity to pathogen entry sites. Virus-specific CX 3 CR1 + memory CD8 + T cells are scarce during chronic infection in humans and mice but increase when infection is controlled spontaneously or by therapeutic intervention. This CX 3 CR1-based functional classification will help to resolve the principles of protective CD8 + T-cell memory. The function of memory CD8 + T cells is often believed to be directly correlated with their localization in tissues. Here the authors show that CD8 + T cells with different proliferative and cytotoxic properties can be distinguished based on their expression of CX3CR1, independently of their tissue localization.