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 fh ) 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 fh cells at the transcriptomic level and demonstrated that the T fh cell program is well-initiated in neonates although the T fh gene-expression pattern (i.e., CXCR5, IL-21, BCL6, TBK1, STAT4, ASCL2 , and c-MAF ) is largely underrepresented as compared to adult T fh cells. Importantly, we identified a TH2-bias of neonatal T fh cells, with preferential differentiation toward short-lived pre-T fh effector cells. Remarkably, adjuvantation with CpG-ODNs redirect neonatal pre-T fh cells toward committed GC-T fh cells, as illustrated by increased expression of T fh signature genes and reduced expression of TH2-related genes.
Authors
Beatris Mastelic-Gavillet; Maria Vono; Patrícia Gonzalez-Dias; Frederico Moraes Ferreira; Lucas Cardozo; Paul-Henri Lambert; Helder I Nakaya; Claire-Anne Siegrist
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Associeted Project
Systems Immunology of Human Diseases
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