Blimp-1 directly represses <i>Il2</i> and the <i>Il2</i> activator <i>Fos</i>, attenuating T cell proliferation and survival

Abstract

Mice with a T cell-specific deletion of Prdm1, encoding Blimp-1, have aberrant T cell homeostasis and develop fatal colitis. In this study, we show that one critical activity of Blimp-1 in T cells is to repress IL-2, and that it does so by direct repression of Il2 transcription, and also by repression of Fos transcription. Using these mechanisms Blimp-1 participates in an autoregulatory loop by which IL-2 induces Prdm1 expression and thus represses its own expression after T cell activation, ensuring that the immune response is appropriately controlled. This activity of Blimp-1 is important for cytokine deprivation-induced T cell death and for attenuating T cell proliferation in antigen-specific responses both in vitro and in vivo.