IL-6 Suppresses Vaccine Responses in Neonatal Mice by Enhancing IL-2 Activity on T Follicular Helper Cells

The inability of neonates to develop CD4+CXCR5+PD−1+ T follicular helper (TFH) cells contributes to their weak vaccine responses. In adult mice, IL-6 promotes TFH-cell expansion by suppressing the expression of IL-2Rβ on TFH cells. Here, we found a totally opposite role for IL-6 in neonatal mice TFH response. Whereas co-injection of neonatal mice with IL-6 and a conjugate polysaccharide vaccine suppressed TFH response by increasing the production of IL-2 and expression of IL-2Rα and IL-2Rβ on TFH cells, immunization of IL-6 knock-out neonatal mice led to improved antibody responses accompanied by expanded TFH cells as well as lower levels of IL-2 and IL-2 receptors on TFH cells. Moreover, CpG containing vaccine improved TFH response in neonates while suppressing the expression of IL-2 receptors on TFH cells, suggesting that CpG protects TFH cells by inhibiting IL-2 activity. These findings unveil age specific differences in IL-6 mediated vaccine responses and highlight the need to consider age related immunobiological attributes in designing vaccines.### Competing Interest StatementThe authors have declared no competing interest.