Extrafollicular Foxp3+regulatory T cells control the initiation of the germinal centre response. (A) During the early germinal centre (GC) response, Foxp3+ regulatory T (Treg) cells promote the immune response by IL-2 consumption. (B) A model of Foxp3+ Treg cell-mediated GC suppression by cytotoxic T-lymphocyte antigen 4 (CTLA-4). CTLA-4 is able to trans-endocytose CD80/86 from the dendritic cell (DC), thereby inhibiting co-stimulatory signalling through CD28 on the CD4+ T cells. Defective T-cell priming will result in failure of follicular helper T (Tfh) cell differentiation. Foxp3, forkhead box p3; MHC-II, major histocompatibility complex class II; TCR, T-cell receptor.