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 found 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 downregulated CD25, upregulated 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.
