Neonatal T Follicular Helper Cells Are Lodged in a Pre-T Follicular Helper Stage Favoring Innate Over Adaptive Germinal Center Responses.

T follicular helper (T) cells have emerged as a critical limiting factor for controlling the magnitude of neonatal germinal center (GC) reactions and primary vaccine antibody responses. We compared the functional attributes of neonatal and adult T cells at the transcriptomic level and demonstrated that the T cell program is well-initiated in neonates although the T gene-expression pattern (i.e., , and ) is largely underrepresented as compared to adult T cells. Importantly, we identified a TH2-bias of neonatal T cells, with preferential differentiation toward short-lived pre-T effector cells. Remarkably, adjuvantation with CpG-ODNs redirect neonatal pre-T cells toward committed GC-T cells, as illustrated by increased expression of T signature genes and reduced expression of TH2-related genes.