Specialized helper cells contribute to immunological memory
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Using single-cell RNA sequencing (scRNAseq) we determined that long-lived TFH cells are transcriptionally distinct from TCM cells, maintain stemness and self-renewal gene expression, and a higher degree of differentiation plasticity compared to TCM cells. Unexpectedly, long-lived TFH cells concurrently expressed a unique metabolic signature similar to that found in trained immune cells, including enrichment of genes regulated by Hif1a, mTOR, and cAMP. These findings were confirmed at the epigenetic level, revealing that TFH cells maintain significantly more open chromatin in the promoter regions of Tcf7 and mTOR regulated genes compared to Th1 memory cells. Importantly, we also demonstrated that long-lived TFH cells actively support antibody production by splenic plasma cells, making a key contribution to systemic antibody titers at very late time points after infection when the immune response has supposedly died down. Taken together, these data highlight memory TFH cells as an attractive target for vaccination.
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Graphical abstract of our TFH paper!
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