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Competing Interests: The authors declare no conflict of interest.

Purpose of Review: T follicular helper (Tfh) cells are an increasingly relevant CD4 T cell subset responsible for the provision of help to B cells for the generation of an effective humoral immune response. Here we review recent studies that have provided critical insights into the mechanisms of Tfh cell differentiation and function, and introduce newly identified roles for Tfh cells in human disease., Recent Findings: Novel molecular regulators of the Tfh cell differentiation program along with new found roles for the costimulatory and coinhibitory inducible T cell costimulator (ICOS), programmed death 1, and cytotoxic T lymphocyte antigen 4 pathways on Tfh cell function have been appreciated. Although circulating Tfh and Tfh-like subset signatures have been linked to numerous immune conditions, extrapolation of these findings to organ transplantation is just beginning., Summary: The combination of recent progress with regard to Tfh cell biology at the basic science and clinical levels is guiding the elucidation of the role of Tfh cells in the alloimmune response. Application of this knowledge toward the development of novel therapeutic strategies for use in transplantation is imminent.