Noncanonical functions of T follicular helper cells

T follicular helper cells (T FH cells) are essential for germinal center (GC) formation and maintenance. However, recent insights reveal that T FH cells play additional immune regulatory roles beyond their traditional B cell helper function. Here, we review the functional and anatomical diversity of T FH cells and their unconventional roles in modulating immune responses during infection, vaccination, allergy, and tolerance. These functions include their stem-like memory T cell properties and their role as reservoirs for effector T cell (T eff cell) precursors. We also summarize the contributions of “ex-T FH cells” to immune homeostasis and the functions of diverse subsets of cytokine-producing T FH cells in aiding CD8 + T cells and regulating critical B cell fate decisions. In summary, this Review underscores the multifaceted contributions of T FH cells to immune regulation, extending beyond their traditional B cell helper roles.