Abstract
SummaryThe early events of CD8 memory generation remain largely unknown. Here we report that as early as 2 days after antigen priming, very early memory precursors can be identified by their expression of the chemokine receptor CXCR5. These early precursors, which have an effector phenotype, expand and temporarily migrate to the T-B cell zone junction where they interact with follicular CD4+ T cells (Tfh). Remarkably, this interaction with Tfh, hitherto considered as exclusive B cell helpers, is required for CD8 memory precursors to become highly competent memory cells. CD40 and interleukin-21 signaling are involved in the help provided to CXCR5+CD8 memory precursors. This study thus unveils critical early steps in the generation of CD8 memory, identifies CXCR5 as the earliest known marker of CD8 memory precursors, suggests a major helper role for Tfh, and points to possible coordination between the pathways of CD8 and B cell memory generation at the T-B-cell zone junction.
Highlights
Following antigen activation, a naive CD8 cell subset undergoes strong clonal expansion, generating a heterogeneous population of activated cells that is dominated, at the peak of expansion, by short-lived CD8 effectors (Kaech and Cui, 2012)
We show that, as early as 2 days after antigen priming, very early memory precursors can be identified by their expression of the chemokine receptor CXCR5
These CXCR5+ precursors migrate to the junction between T and B cell zones, where they receive critical help from follicular CD4+ T cells (Tfh), a specialized CD4+ T cell subset hitherto considered as exclusive B cell helpers (Crotty, 2011; Vinuesa et al, 2016)
Summary
A naive CD8 cell subset undergoes strong clonal expansion, generating a heterogeneous population of activated cells that is dominated, at the peak of expansion, by short-lived CD8 effectors (Kaech and Cui, 2012) This expansion is followed by a phase of drastic contraction through massive apoptosis. We show that, as early as 2 days after antigen priming, very early memory precursors can be identified by their expression of the chemokine receptor CXCR5 These CXCR5+ precursors migrate to the junction between T and B cell zones, where they receive critical help from follicular CD4+ T cells (Tfh), a specialized CD4+ T cell subset hitherto considered as exclusive B cell helpers (Crotty, 2011; Vinuesa et al, 2016). Tfh enable these CXCR5+ precursors to become highly competent memory cells
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