Dynamic regulation of T Follicular Regulatory cell responses by interleukin 2 during influenza infection

Interleukin 2 (IL-2) promotes Foxp3(+)-regulatory T (T(reg)) cell responses, but inhibits T follicular helper (T(FH)) cell development. However, it is not clear how IL-2 affects T follicular regulatory (T(FR)) cells, a cell type with properties of both T(reg) and T(FH) cells. Using an influenza infection model, we demonstrated that high IL-2 concentrations at the peak of the infection prevented T(FR) cell development by a Blimp-1–dependent mechanism. However, once the immune response resolved, some T(reg) cells down-regulated CD25, up-regulated Bcl-6 and differentiated into T(FR) cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones. Thus, unlike its effects on conventional T(reg) cells, IL-2 inhibits T(FR) cell responses.