FoxP3(+) regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability

Here we test the role of FoxP3(+) regulatory T cells (Tregs) in controlling T follicular helper (Tfh) and germinal-center (GC) B cell responses to influenza. In contrast to the idea that Tregs suppress T cell responses, we find that Treg depletion severely reduces the Tfh cell response to influenza virus. Furthermore, Treg depletion prevents the accumulation of influenza-specific GCs. These effects are not due to alterations in TGFβ availability or a precursor-progeny relationship between Tregs and Tfh cells, but are instead mediated by increased availability of IL-2, which suppresses the differentiation of Tfh cells and as a consequence, compromises the GC B response. Thus, Tregs promote influenza-specific GC responses by preventing excessive IL-2 signaling, which suppresses Tfh cell differentiation.