Regulatory T cells, particularly their follicular resident subset, T-follicular regulatory cells, play a critical role in the maintenance of immune homeostasis and prevention of the expansion of T-follicular helper cells. One of the key mechanisms used by these cells is CTLA-4 dependent suppression of inflammation. In this chapter, we detail methods to increase the formation of T-follicular helper cells following vaccination by either depleting Treg cells, via Foxp3 linked diphtheria toxin receptor, or blocking CTLA-4 function by the use of antibodies.