T follicular helper cells and their impact on humoral responses during pathogen and vaccine challenge

T follicular helper (Tfh) cells are essential for the establishment, maintenance and output of the germinal centre (GC) response. The transient nature of this response, and its location within secondary lymphoid tissues have hampered our understanding of this critical cell type, particularly in humans. A counterpart of GC Tfh cells in peripheral blood has enabled recent discoveries in disease and vaccination settings, while direct sampling of lymph nodes provides exciting new avenues to study GC responses directly in vivo. Tfh differentiation is shaped by the cytokine milieu during inflammation, vaccination and with age, and disease-specific patterns are emerging. An improved understanding of how to support a Tfh response remains key to enhancing vaccine immunity across the lifespan.