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.
Highlights
The most effective vaccines in use today rely on the long-term protection elicited by high-affinity memory B cells and long-lived plasma cells, which are associated with germinal centers (GC) [1]
To address whether IFN-α up-regulates the generation of memory Tfh cells, BALB/c mice were immunized with either adenoviral vectors expressing foot-and-mouth disease virus (FMDV) VP1 alone or co-expressing VP1 and IFN-a
The splenocytes were harvested on days 30, 60, and 90 after immunization, and the activated CD4+ T cells, memory CD4+ T cells, and memory Tfh cells (CXCR5+CD4+) were enumerated and characterized by multiple-color flow cytometry
Summary
The most effective vaccines in use today rely on the long-term protection elicited by high-affinity memory B cells and long-lived plasma cells, which are associated with germinal centers (GC) [1]. Tfh cells themselves express IL-21 receptors, affecting the differentiation and migration of Tfh cells via autocrine signaling [10, 11]. Because of their central role in the production of long-lasting humoral immunity, Tfh cells represent an interesting target for rational vaccine design. Novel or modified adjuvants may prove to be an effective strategy for skewing helper T cell differentiation toward the Tfh cell subset and promoting GC responses. Our previous work revealed the potent adjuvant activity of IFNα, which enhanced the generation of Tfh cells and regulated humoral immunity by promoting GC reactions and antibody responses [14]
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