1IFN-α Modulates Memory Tfh Cells and Memory B Cells in Mice, Following Recombinant FMDV Adenoviral Challenge
Xiangguo Duan, Peng Sun, Yaru Lan, Chunxiu Shen, Xiaoyu Zhang, Shaozhang Hou, Jian Chen, Bin Ma, Yuhan Xia, Chunxia Su
Abstract
Follicular helper T (Tfh) cells regulate high-affinity antibody production. Some findings have indicated that Tfh cells could be differentiated into memory cells. Here we have investigated the effects of IFN-α, as an adjuvant, on the generation of memory Tfh cell and memory B cell responses. The data showed that adenoviral vectors expressing: i) foot-and-mouth disease virus (FMDV) VP1 proteins and porcine IFN-α, or ii) porcine IFN-α alone, potently enhanced the generation of memory Tfh cells, especially the CCR7lo memory Tfh subset. Upon rechallenge with FMD recombinant adenoviral vaccines, IFN-α enhances Tfh cells activity, rapidly upregulating their signature Bcl-6, CXCR5, and IL-21 markers. The results suggest that IFN-α enhances the levels of the transcription factor Bcl-6 within Tfh cells, potentially by regulating STAT1. Additionally, IFN-α substantially increased the number of IgG1+ and CD86+ memory B cells, which are responsible for inducing the rapid effector functions of memory Tfh cells after vaccine reactivation, establishing the close relationship between memory B cell and memory Tfh cell subsets. In brief, IFN-α enhances the potency of FMD recombinant adenoviral vaccines to induce memory Tfh and memory B cell responses, thus elevating serum antibody titers. IFN-α administration therefore represents an attractive strategy for enhancing responses to vaccination.