IL-6 suppresses vaccine responses in neonatal mice by enhancing IL-2 activity on T follicular helper cells

Abstract

AbstractThe 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 TFHcells. Here, we found a totally opposite role for IL-6 in neonatal mice TFHresponse. Whereas co-injection of neonatal mice with IL-6 and a conjugate polysaccharide vaccine suppressed TFHresponse by increasing the production of IL-2 and expression of IL-2Rα and IL-2Rβ on TFHcells, immunization of IL-6 knock-out neonatal mice led to improved antibody responses accompanied by expanded TFHcells as well as lower levels of IL-2 and IL-2 receptors on TFHcells. Moreover, CpG containing vaccine improved TFHresponse in neonates while suppressing the expression of IL-2 receptors on TFHcells, suggesting that CpG protects TFHcells 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.