Early commitment of naïve human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL‐12

T follicular helper (T FH ) cells are a specialized subset of CD4 + T cells that localize to B‐cell follicles, where they are positioned to provide help for the induction of optimal humoral immune responses. Key features of T FH cells are the expressions of CXCR5, ICOS, interleukin (IL)‐21 and BCL‐6 . The requirements for human T FH cell development are unknown. Here we show that IL‐6, IL‐12, IL‐21 and IL‐23 are capable of inducing IL‐21 expression in naïve CD4 + T cells isolated from human tonsils, peripheral blood and cord blood. However, only IL‐12 induced sustained expressions of CXCR5 and ICOS on these activated naïve CD4 + T cells, and endowed them with the ability to provide increased help to B cells for their differentiation into immunoglobulin‐secreting cells. The effects of IL‐12 were independent of interferon‐γ and T‐bet, and associated with upregulation of BCL‐6 expression. Thus, these cytokines, particularly IL‐12, are likely to act at an early stage during dendritic cell‐mediated priming of naïve CD4 + T cells into a T FH cell fate, and thus underpin antibody‐mediated immunity.