The regulation of T follicular helper responses during infection

Following infection, naïve CD4 T cells can differentiate into various functionally distinct effector and memory subsets, including T follicular helper (TFH) cells that orchestrate germinal center (GC) reactions necessary for high-affinity, pathogen-specific antibody responses. The origins and function of this cell type have been extensively examined in response to subunit immunization with model antigens. More recently, we are beginning to also appreciate the extent to which microbial infections shape the generation, function and maintenance of TFH cells. Here, we review recent advances and highlight additional knowledge gaps in our understanding of how microbial infections influence priming, differentiation, localization and activity of TFH cells following acute and chronic infections.