OA16.06
Background: Peripheral blood CD4+ T follicular helper (pTfh) cells were recently identified in humans, but it is unclear whether they resemble a stable population of antigen-specific memory cells responsive upon antigen re-encounter. We investigated pTfh kinetics, population diversity and their relationship to B-cell responses in vaccine recipients.
Methods: PBMC samples, longitudinally collected from volunteers enrolled in HVTN068 from either the DNA/Ad5 or Ad5/Ad5 arm as well as from healthy, non-vaccinated donors were used to identify three distinct CXCR5+pTfh subsets by their individual expression pattern of PD1 and ICOS. Multicolor flow cytometry, qPCR and deep sequencing of the TCRB repertoire of individual CD4+ T cell subsets was applied to characterize and phenotype the individual pTfh subsets.
Results: Amongst the different pTfh subsets, the vaccine-specific PD1/ICOS double-positive memory pTfh (pTfhdp) showed a unique clonal expansion one week after boosting. Simultaneously, vaccine-specific, IgG expressing plasmablasts appeared in the circulation. At the same time, proliferating pTfhdp cells up-regulated germinal center Tfh genes, and became enriched for Th1-like cells. Strikingly, during the peak response the T-cell receptor clonal repertoire of pTfhdp was completely exchanged and identical T-cell clones were shared with PD1+ICOS- memory pTfh (pTfhPD1) cells.
Conclusions: We conclude that vaccination induces memory pTfhPD1 that respond with a rapid but transient expansion and differentiation into activated pTfhdp following antigen re-encounter.
