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bioRxiv · 10.1101/2022.10.31.514554

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

Parvathaneni, S.·Yang, J.·Lotspeich-Cole, L.·Sakai, J.·Lee, R. C.·Akkoyunlu, M.
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Abstract

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-2R{beta} 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-2R and IL-2R{beta} 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.

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Parvathaneni, S., Yang, J., Lotspeich-Cole, L., Sakai, J., Lee, R. C., Akkoyunlu, M.. 2022-11-01. IL-6 suppresses vaccine responses in neonatal mice by enhancing IL-2 activity on T follicular helper cells. https://doi.org/10.1101/2022.10.31.514554

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